Process for the manufacture of alkylfluoroacrylate

Abstract

The invention relates to a process for the manufacture of an alkylfluoroacrylate starting from alkylfluoroacetate and an oxalic acid ester, wherein an alkane liquid under the reaction conditions is applied as the solvent in one of the reaction steps.

Claims

1. A process for the manufacture of an alkylfluoroacrylate, comprising the following steps: A. an alkylfluoroacetate with an ester of oxalic acid is reacted in the presence of sodium methoxide in methanol and a suitable solvent in a crossed Claisen condensation reaction resulting in a Claisen salt; B. the Claisen salt obtained in step A is optionally filtered off and washed with a suitable solvent; C. the Claisen salt obtained in step A or B is reacted with paraformaldehyde in a suitable solvent; D. the alkylfluoroacrylate obtained in step C is isolated using a suitable solvent; wherein the alkylfluoroacrylate is methylfluoroacrylate or ethylfluoroacrylate; wherein the solvent in at least steps C and D and optionally in one of steps A or B is an alkane selected from a group consisting of pentane and hexane.

2. The process according to claim 1, wherein the alkane is pentane.

3. The process according to claim 1, wherein the ester of oxalic acid is dimethyloxalate.

4. The process according to claim 1, wherein the solvent in step A is methyl-tert-butylether or pentane.

5. The process according to claim 1, wherein alkylfluoroacrylate obtained after the reaction with paraformaldehyde is quenched with water before isolation.

6. The process according to claim 1, wherein the isolation comprises a filtration and a distillation.

Description

EXAMPLES

Comparative Example A: Original Process

(1) Sodium hydride (NaH) (60% in oil, 20.9 g, 1.2 equiv.) and methyl-tert-butyl-ether (MTBE) (100 mL) were charged to the reactor at room temperature. Catalytic amount of methanol (0.8 mL) was added dropwise and the suspension was heated to 30° C.

(2) Step A

(3) In a separate reactor dimethyl oxalate (51.5 g, 1.1 equiv.) was dissolved in MTBE (350 mL) and methyl fluoroacetate (MFAc) (40.0 g) was added. Resulting solution was added over 10-12 hours to a suspension of sodium hydride in MTBE at 30-35° C. The resulting slurry was stirred for additional 12 h at 30-35° C. then cooled to 5-10° C.

(4) Step C

(5) Paraformaldehyde (15.7 g, 1.2 equiv.) was added in 10 portions and the suspension was stirred at 5-10° C. for additional 5 h. The solid was filtered off and washed with MTBE (150 mL). The filtrate (acrylate) was distilled in vacuum with column (Sulzer, 8 theoretical plates) to remove MTBE and subsequently MFA was distilled at 40° C./100-75 mbar.

(6) There was 58% yield prior to distillation, leading to 35-40% isolated yield after distillation. However, off-spec product was obtained because of residual methyl fluoroacetate and dimethyl carbonate (0.7 wt % methyl fluoroacetate, 3.3 wt % dimethyl carbonate).

Comparative Example B: Isolation of Claisen Salt (Removal of Residual Methyl Fluoroacetate and Dimethyl Carbonate)

(7) Step A

(8) NaH (60% in oil, 20.9 g, 1.2 equiv.) and MTBE (100 mL) were charged to the reactor at room temperature. Catalytic amount of methanol (0.8 mL) was added dropwise and the suspension was heated to 30° C.

(9) In a separate reactor dimethyl oxalate (51.5 g, 1.1 equiv.) was dissolved in MTBE (350 mL) and methyl fluoroacetate was added. Resulting solution was added over 10-12 hours to a suspension of sodium hydride in MTBE at 30-35° C.

(10) Step B

(11) The suspension was cooled to 10° C. and the Claisen salt was filtered off. The filter cake was washed twice with MTBE (2×150 mL).

(12) Step C

(13) The wet salt and MTBE (300 mL) was charged to the reactor and the suspension was cooled to 5-10° C. Paraformaldehyde (15.7 g, 1.2 equiv.) was added in 10 portions and the suspension was stirred at 5-10° C. for additional 5 h.

(14) Step D

(15) The solid was filtered off and washed with MTBE (150 mL). The filtrate (acrylate) was analyzed by GC.

(16) There was 60% yield prior to distillation and after distillation there was 35-40% isolated yield of in-spec product, i.e. there was no unreacted methyl fluoroacetate and dimethyl carbonate.

(17) In addition MTBE as solvent complicate isolation of acrylate, as distillation needs to be carried out at temperature<45° C. for safety reasons (otherwise spontaneous, very exothermic polymerization can take place). Therefore vacuum distillation is required, which worsens separation of acrylate from MTBE (boiling point of MFA is 90.5°-91.75 C at atmospheric pressure).

Comparative Example C: Claisen Condensation with NaOMe in Methanol

(18) Step A

(19) Solid sodium methoxide (14.8 g, 1.2 equiv.) was dissolved in methanol (150 mL) at 0-20° C. and dimethyl oxalate (28.2 g, 1.1 equiv.) was added. The mixture was stirred for 15 min at 20-25° C. followed by addition of methyl fluoroacetate (20.0 g). Resulting solution was heated to 30° C. and stirred at 30° C. for 24 h.

(20) Step C

(21) The reaction mixture was cooled to 10-15° C. and paraformaldehyde was added in several portions. Resulting suspension was warmed to 25° C. and stirred for additional 1 hour.

(22) The suspension was analyzed by GC.

(23) Only 58% conversion of methyl fluoroacetate was reached.

Comparative Example D: Claisen Condensation with NaOMe in MTBE

(24) Step A

(25) Solid sodium methoxide (14.8 g, 1.2 equiv.) was suspended in MTBE (250 mL) at 20-25° C. and dimethyl oxalate (28.2 g, 1.1 equiv.) was added. The suspension was stirred for 15 min at 20-25° C. followed by slow addition of methyl fluoroacetate (20.0 g). Resulting thick slurry was heated to 30° C. and stirred at 30° C. for 24 h.

(26) Step C

(27) The reaction mixture was cooled to 10-15° C. and paraformaldehyde was added in several portions. Resulting suspension was warmed to 25° C. and stirred for additional 1 hour.

(28) The suspension was analyzed by GC.

(29) Only 78% conversion of methylfluoroacetate was reached.

Comparative Example E: Claisen Condensation with 30% NaOMe Solution in MTBE

(30) Step A

(31) Dimethyl oxalate (14.7 g, 1.1 equiv.) was dissolved in MTBE (140 mL) at 20-25° C. followed by addition of methyl fluoroacetate (10.0 g). The mixture was stirred for 15 min at 20-25° C. and 30% NaOMe solution in methanol (24.3 g, 1.25 equiv.) was added dropwise.

(32) Step B

(33) The resulting solution was stirred for 45 h at 20-25° C. (crystallization observed after 2 h at 20-25° C.). The suspension was cooled to 10° C., the Claisen salt was filtered off and washed twice with MTBE (2×40 mL).

(34) Step C

(35) The wet salt and MTBE (70 mL) was charged to the reactor and the suspension was cooled to 5-10° C. Paraformaldehyde (4.0 g, 1.2 equiv.) was added in 10 portions and the suspension was stirred at 5-10° C. for additional 5 h.

(36) Step D

(37) The reaction mixture was quenched with water (63 mL) and the aqueous phase extracted once with MTBE (90 mL).

(38) Combined organic phase was analyzed by quantitative GC. With this reaction 95% conversion of methylfluoroacetate was reached. The yield was 70% of in-spec methyl fluoroacrylate prior to distillation.

Example 1: Isolation of Methyl Fluoroacrylate from Pentane

(39) Step A

(40) NaH (60% in oil, 20.9 g, 1.2 equiv.) and MTBE (100 mL) were charged to the reactor at room temperature. Catalytic amount of methanol (0.8 mL) was added dropwise and the suspension was heated to 30° C.

(41) In a separate reactor dimethyl oxalate (51.5 g, 1.1 equiv.) was dissolved in MTBE (350 mL) and methyl fluoroacetate was added. Resulting solution was added over 10-12 hours to a suspension of sodium hydride in MTBE at 30-35° C.

(42) Step B

(43) The suspension was cooled to 20° C. and the Claisen salt was filtered off. The filter cake was washed twice with MTBE (2×100 mL) and three times with pentane (3×150 mL).

(44) Step C

(45) The wet salt and pentane (300 mL) was charged to the reactor and the suspension was cooled to 5-10° C. Paraformaldehyde (15.7 g, 1.2 equiv.) was added in 10 portions and the suspension was stirred at 5-10° C. for additional 5 h.

(46) Step D

(47) The solid was filtered off and washed with pentane (150 mL). The filtrate (acrylate) was distilled in vacuum with column (Sulzer, 8 theoretical plates) to remove MTBE and subsequently MFA was distilled at 40° C./100-75 mbar.

(48) There was 67% yield prior to distillation and after distillation there was 50% isolated yield of in-spec product, i.e. unreacted methyl fluoroacetate and dimethylcarbonate were not present in isolated product.

Example 2: Claisen Condensation with 30% NaOMe Solution in Pentane

(49) Step A

(50) Dimethyl oxalate (28.2 g, 1.1 equiv.) was suspended in pentane (100 mL) at 20-25° C. followed by addition of methyl fluoroacetate (20.0 g). The mixture was stirred for 15 min at 20-25° C. (two clear phases) and 30% NaOMe solution in methanol (48.9 g, 1.25 equiv.) was added dropwise. The resulting turbid solution was stirred for 24 h at 20-25° C. (crystallization observed after 2 h at 20-25° C.).

(51) Step B

(52) The suspension was cooled to 0° C., the Claisen salt was filtered off and washed with pentane (3×40 mL).

(53) Step C

(54) The wet salt and pentane (120 mL) was charged to the reactor and the suspension was cooled to 5-10° C. Paraformaldehyde (4.0 g, 1.2 equiv.) was added in 10 portions and the suspension was stirred at 5-10° C. for additional 5 h.

(55) Step D

(56) The reaction mixture was quenched with water (115 mL) and the aqueous phase extracted once with pentane (2×60 mL). Combined organic phase was analyzed by quantitative GC.

(57) With this reaction 93% conversion of methyl fluoroacetate was reached. The yield was 66% prior to distillation. Methyl fluoroacrylate was isolated in a yield of 58% after distillation.

Example 3: Claisen Condensation with Less 30% NaOMe Solution in Less Pentane as Compared to Example 2

(58) Step A

(59) Dimethyl oxalate (28.2 g, 1.1 equiv.) was suspended in pentane (40 mL) at 20-25° C. followed by addition of methyl fluoroacetate (20.0 g). The mixture was stirred for 15 min at 20-25° C. (two clear phases) and 30% NaOMe solution in methanol (41.0 g, 1.05 equiv.) was added dropwise. The resulting turbid solution was stirred for 24 h at 20-25° C. (crystallization observed after 2 h at 20-25° C.).

(60) Step B

(61) The suspension was cooled to 0° C., the Claisen salt was filtered off and washed with pentane (3×40 mL).

(62) Step C

(63) The wet salt and pentane (120 mL) was charged to the reactor and the suspension was cooled to 5-10° C. Paraformaldehyde (4.0 g, 1.2 equiv.) was added in 10 portions and the suspension was stirred at 5-10° C. for additional 5 h.

(64) Step D

(65) The reaction mixture was quenched with water (115 mL) and the aqueous phase extracted once with pentane (2×60 mL). Combined organic phase was analyzed by quantitative GC.

(66) With this reaction 90% conversion of methyl fluoroacetate was reached. The yield was 65% prior to distillation. Methyl fluoroacrylate was isolated in a yield of 55% after distillation.

Hypothetical Example 4: Claisen Condensation with 30% NaOMe Solution in Hexane

(67) Step A

(68) Dimethyl oxalate (28.2 g, 1.1 equiv.) is suspended in hexane (40 mL) at 20-25° C. followed by addition of methyl fluoroacetate (20.0 g). The mixture is stirred for 15 min at 20-25° C. (two clear phases) and 30% NaOMe solution in methanol (48.9 g, 1.25 equiv.) is added dropwise. The resulting turbid solution is stirred for 24 h at 20-25° C.

(69) Step B

(70) The suspension is cooled to 0° C., the Claisen salt is filtered off and washed with hexane (3×40 mL).

(71) Step C

(72) The wet salt and hexane (120 mL) are charged to the reactor and the suspension is cooled to 5-10° C. Paraformaldehyde (4.0 g, 1.2 equiv.) is added in 10 portions and the suspension is stirred at 5-10° C. for additional 5 h.

(73) Step D

(74) The reaction mixture is quenched with water (115 mL) and the aqueous phase extracted once with hexane (2×60 mL). Organic phases are combined and the product is purified by vacuum distillation.

(75) The yield reached prior to distillation is expected to be in line with the yields obtained for the pentane examples.

Hypothetical Example 5: Claisen Condensation of Ethyl Fluoroacetate with 30% NaOMe Solution in Pentane

(76) Step A

(77) Diethyl oxalate (34.9 g, 1.1 equiv.) is suspended in pentane (40 mL) at 20-25° C. followed by addition of ethyl fluoroacetate (23.0 g). The mixture is stirred for 15 min at 20-25° C. and 30% NaOMe solution in methanol (48.9 g, 1.25 equiv.) is added dropwise. The resulting solution is stirred for 24 h at 20-25° C.

(78) Step B

(79) The suspension is cooled to 0° C., the Claisen salt is filtered off and washed with pentane (3×40 mL).

(80) Step C

(81) The wet salt and pentane (120 mL) are charged to the reactor and the suspension is cooled to 5-10° C. Paraformaldehyde (4.0 g, 1.2 equiv.) is added in 10 portions and the suspension is stirred at 5-10° C. for additional 5 h.

(82) Step D

(83) The reaction mixture is quenched with water (115 mL) and the aqueous phase extracted once with pentane (2×60 mL). Organic phases are combined and the product is purified by vacuum distillation.

(84) The yield reached prior to distillation is expected to be in line with the yield obtained for the methylfluoroacrylate examples.