N-FLUOROALKYL COMPOUND PRODUCTION METHOD

Abstract

Provided is a production method comprising step A of reacting a compound represented by Formula (2):

##STR00001##

wherein R.sup.1, R.sup.2, and R.sup.3 are the same or different, R.sup.1 represents COR, R.sup.2 and R.sup.3 each represent a hydrogen atom or COR, and R.sup.4 represents a C.sub.1-C.sub.12 alkyl group or a C.sub.6-C.sub.12 aryl group; with a fluorinating agent containing IF.sub.5, an amine, and HF at 80 C. or lower throughout the reaction from the start to the end. This production method is capable of synthesizing a compound (N-fluoroalkylated hydrazine derivative) represented by formula (1):

##STR00002##

wherein R.sup.1, R.sup.2, and R.sup.3 are as defined above, wherein Rs are the same or different and each represents a C.sub.1-C.sub.12 alkoxy group optionally substituted with one or more substituents or a C.sub.6-C.sub.12 aryloxy group optionally substituted with one or more substituents.

Claims

1. A method for producing a compound represented by formula (1): ##STR00032## wherein R.sup.1, R.sup.2, and R.sup.3 are the same or different, R.sup.1 represents COR, and R.sup.2 and R.sup.3 each represent a hydrogen atom or COR, wherein Rs are the same or different and each represents a C.sub.1-C.sub.12 alkoxy group optionally substituted with one or more substituents or a C.sub.6-C.sub.12 aryloxy group optionally substituted with one or more substituents; the method comprising step A of reacting a compound represented by formula (2): ##STR00033## wherein R.sup.1, R.sup.2, and R.sup.3 are as defined above, and R.sup.4 represents a C.sub.1-C.sub.12 alkyl group or a C.sub.6-C.sub.12 aryl group, with a fluorinating agent containing IF.sub.5, an amine, and HF at 80 C. or lower throughout the reaction from the start to the end.

2. The production method according to claim 1, wherein in formulas (1) and (2), R.sup.1 represents a tert-butyloxycarbonyl group, a benzyloxycarbonyl group, a (2,2,2-trichloroethoxy) carbonyl group, an ethoxycarbonyl group, or an isopropoxycarbonyl group, and R.sup.2 and R.sup.3 are the same or different and each represents a hydrogen atom, a tert-butyloxycarbonyl group, a benzyloxycarbonyl group, a (2,2,2-trichloroethoxy) carbonyl group, an ethoxycarbonyl group, or an isopropoxycarbonyl group.

3. The production method according to claim 1, wherein the compound represented by formula (2) is ##STR00034##

4. The production method according to claim 3, wherein the compound represented by formula (2) is ##STR00035##

5. The production method according to claim 1, wherein the compound represented by formula (1) is ##STR00036##

6. The production method according to claim 5, wherein the compound represented by formula (1) is ##STR00037##

7. The production method according to claim 1, wherein step A is carried out at a reaction temperature of 10 to 40 C.

8. The production method according to claim 1, wherein step A is carried out in the presence of a solvent.

9. The production method according to claim 8, wherein the solvent is at least one member selected from the group consisting of (cyclo)alkanes, chlorine-containing organic solvents, aromatic solvents, nitrile-containing organic solvents, fluorine-containing organic solvents, and ester-containing organic solvents.

Description

EXAMPLES

[0107] The features of the present disclosure are described in more detail below with reference to Examples. However, the present disclosure is not limited to the embodiments of these Examples.

Examples 1 to 5

##STR00026##

[0108] In the formula, Boc represents a tert-butyloxycarbonyl group, and Me represents a methyl group.

Example 1

[0109] Toluene (1.3 g) was added to a reactor, followed by the addition of raw material compound 1 (1.3 g, 4.03 mmol). While stirring, IF.sub.5-Et.sub.3N-3HF (1.54 g, 4.03 mmol) was added thereto dropwise and reacted at room temperature for 16 hours (during the dropwise addition and reaction, the reaction liquid generates heat; therefore, the external temperature was adjusted to maintain the internal temperature at 10 C. to 40 C.). After terminating the reaction with an aqueous potassium hydroxide solution, the yield of target compound 2 was confirmed to be 70% by F-NMR.

Example 2

[0110] The reaction was carried out in the same manner as in Example 1, except that the solvent was changed from toluene to dichloromethane, thereby obtaining target compound 2 in a yield of 66%.

Example 3

[0111] The reaction was carried out in the same manner as in Example 1, except that the solvent was changed from toluene to n-heptane, thereby obtaining target compound 2 in a yield of 59%.

Example 4

[0112] The reaction was carried out in the same manner as in Example 1, except that the solvent was changed from toluene to ethyl acetate, thereby obtaining target compound 2 in a yield of 48%.

Example 5

[0113] The reaction was carried out in the same manner as in Example 1, except that the solvent was changed from toluene to acetonitrile, thereby obtaining target compound 2 in a yield of 53%.

Comparative Example 1

[0114] The reaction was carried out in the same manner as in Example 1, except that IF.sub.5-Et.sub.3N-3HF was added while stirring the reaction liquid at room temperature (internal temperature: 27 C.), without adjusting the external temperature. It was confirmed that the internal temperature increased to 95 C. Consequently, target compound 2 was obtained in a yield of 15%.

Example 6

##STR00027##

[0115] In the formula, Boc represents a tert-butyloxycarbonyl group, and Me represents a methyl group.

[0116] Toluene (1.7 g) was added to a reactor, followed by the addition of raw material compound 3 (1.7 g, 4.03 mmol). While stirring, IF.sub.5-Et.sub.3N-3HF (1.85 g, 4.84 mmol) was added thereto dropwise and reacted at room temperature for 19 hours (during the dropwise addition and reaction, the reaction liquid generates heat; therefore, the external temperature was adjusted to maintain the internal temperature at 10 C. to 40 C.). After terminating the reaction with an aqueous potassium hydroxide solution, the yield of target compound 4 was confirmed to be 27% by F-NMR.

Example 7

##STR00028##

[0117] In the formula, Cbz represents a benzyloxycarbonyl group, and Me represents a methyl group.

[0118] Dichloromethane (290 g) was added to a reactor, followed by the addition of raw material compound 5 (1.82 g, 4.03 mmol). While stirring, IF.sub.5-Et.sub.3N-3HF (3.87 g, 10.1 mmol) was added thereto dropwise and reacted at room temperature for 14.5 hours (during the dropwise addition and reaction, the reaction liquid generates heat; therefore, the external temperature was adjusted to maintain the internal temperature at 10 C. to 40 C.). After terminating the reaction with an aqueous potassium hydroxide solution, the yield of target compound 6 was confirmed to be 23% by F-NMR.

Example 10 to 11

##STR00029##

[0119] In the formula, Troc represents a (2,2,2-trichloroethoxy) carbonyl group, and Me represents a methyl group.

Example 10

[0120] Dichloromethane (7.3 g) was added to a reactor, followed by the addition of raw material compound 7 (2.61 g, 4.03 mmol). While stirring, IF.sub.5-Et.sub.3N-3HF (6.95 g, 18.1 mmol) was added thereto dropwise and reacted at room temperature for 25 hours (during the dropwise addition and reaction, the reaction liquid generates heat; therefore, the external temperature was adjusted to maintain the internal temperature at 10 C. to 40 C.). After terminating the reaction with an aqueous potassium hydroxide solution, the yield of target compound 8 was confirmed to be 25% by F-NMR.

Example 11

[0121] The reaction was carried out in the same manner as in Example 10, except that the reaction temperature was maintained at an internal temperature of 50 C. to 60 C. instead of 10 C. to 40 C., and that the solvent was changed from dichloromethane to 1,2-dichloroethane, thereby obtaining target compound 8 in a yield of 22%.

Example 12

##STR00030##

[0122] In the formula, Et represents an ethyl group, and Me represents a methyl group.

[0123] Dichloromethane (200 g) was added to a reactor, followed by the addition of raw material compound 9 (1.32 g, 4.03 mmol). While stirring, IF.sub.5-Et.sub.3N-3HF (2.78 g, 7.25 mmol) was added thereto dropwise and reacted at room temperature for 18.5 hours (during the dropwise addition and reaction, the reaction liquid generates heat; therefore, the external temperature was adjusted to maintain the internal temperature at 10 C. to 40 C.). After terminating the reaction with an aqueous potassium hydroxide solution, the yield of target compound 10 was confirmed to be 23% by F-NMR.

Example 13

##STR00031##

[0124] In the formula, Me represents a methyl group.

[0125] Dichloromethane (200 g) was added to a reactor, followed by the addition of raw material compound 11 (1.44 g, 4.03 mmol). While stirring, IF.sub.5-Et.sub.3N-3HF (3.70 g, 9.67 mmol) was added thereto dropwise and reacted at room temperature for 18.5 hours (during the dropwise addition and reaction, the reaction liquid generates heat; therefore, the external temperature was adjusted to maintain the internal temperature at 10 C. to 40 C.). After terminating the reaction with an aqueous potassium hydroxide solution, the yield of target compound 12 was confirmed to be 22% by F-NMR.