PROCESS FOR PREPARING AMINOFURANES

Abstract

The present invention relates to a novel method for preparing 4-aminofurans of the general formula (I) and salts thereof.

Claims

1. A method for preparing a compound of formula (I) and/or salt thereof, ##STR00008## in which R.sup.1 is CF.sub.3, CF.sub.2H, C.sub.2F.sub.5, CF.sub.2Cl, CCl.sub.3, COO(C.sub.1-C.sub.4)alkyl, COOH, R.sup.2 is H, CH.sub.3CO, CCl.sub.3CO, CF.sub.3CO, phenyl-CO, CH.sub.3OCO, (CH.sub.3).sub.3COCO, phenyl, phenyl-CH.sub.2, (diphenyl)CH, Comprising converting a compound of formula (II) ##STR00009## in which R.sup.3 and R.sup.4 are each independently H and C.sub.1-C.sub.4-alkyl and R.sup.1 has the definitions specified above, with aid of an amine of formula R.sup.5-NH.sub.2 (V) to a compound of formula (III) ##STR00010## in which R.sup.5 is H, phenyl, phenyl-CH.sub.2, (diphenyl)CH, and then reacting said compound of formula III in presence of a dehydrating reagent to give a compound of formula (I).

2. The method according to claim 1, wherein definitions of radicals of compounds of formulae (I), (II), (III), (IV) and (V) are as follows: R.sup.1 is CF.sub.3, CF.sub.2H, CF.sub.2Cl, C.sub.2F.sub.5, CCl.sub.3, COOCH.sub.3, COOC.sub.2H.sub.5, R.sup.2 is H, CF.sub.3CO, CH.sub.3CO, CCl.sub.3CO, phenyl, phenyl-CH.sub.2, (diphenyl)CH, CH.sub.3OCO, (CH.sub.3).sub.3COCO, R.sup.3 and R.sup.4 are each independently H or CH.sub.3, R.sup.5 is H, phenyl, phenyl-CH.sub.2, (diphenyl)CH.

3. The method according to claim 1, wherein definitions of radicals of compounds of formulae (I), (II), (III), (IV) and (V) are as follows: R.sup.1 is CF.sub.3, CF.sub.2H, CCl.sub.3, COOCH.sub.3, COOC.sub.2H.sub.5, R.sup.2 is H, COCF.sub.3, COCH.sub.3, COCCl.sub.3, phenyl-CH.sub.2, (diphenyl)CH, CH.sub.3OCO, (CH.sub.3).sub.3COCO, R.sup.3 and R.sup.4 are each independently H or CH.sub.3, R.sup.5 is H.

4. The method according to claim 1, wherein definitions of radicals of compounds of formulae (I), (II), (III), (IV) and (V) are as follows: R.sup.1 is CF.sub.3, COOCH.sub.3, COOC.sub.2H.sub.5, R.sup.2 is H, COCF.sub.3, (CH.sub.3).sub.3COCO, R.sup.3 and R.sup.4 are CH.sub.3 R.sup.5 is H.

5. The method according to claim 1, wherein definitions of radicals of compounds of formulae (I), (II), (III), (IV) and (V) are as follows: R.sup.1 is COOCH.sub.3, COOC.sub.2H.sub.5, R.sup.2 is H, R.sup.3 and R.sup.4 are CH.sub.3, R.sup.5 is H.

6. The method according to claim 1, wherein definitions of radicals of compounds of formulae (I), (II), (III), (IV) and (V) are as follows: R.sup.1 is COOCH.sub.3, R.sup.2 is H, R.sup.3 and R.sup.4 are CH.sub.3, R.sup.5 is H.

7. The method according to claim 1, wherein the reaction is carried out at room temperature.

8. The method according to claim 1, wherein the solvent is methanol, ethanol, isopropanol, butanol, acetonitrile, N,N-dimethylacetamide, toluene or chlorobenzene.

9. The method according to claim 1, wherein the dehydrating reagent is SOCl.sub.2, POCl.sub.3, PCl.sub.3, phosgene, diphosgene, triphosgene, ClCOCOCl, (CF.sub.3CO).sub.2, P.sub.4O.sub.10, SO.sub.2F.sub.2, trimethyl orthoformate and triethyl orthoformate or HCl.

10. The method according to claim 1, wherein the dehydrating reagent is SOCl.sub.2, POCl.sub.3, PCl.sub.3, phosgene, diphosgene, triphosgene or ClCOCOCl.

11. The method according to claim 1, wherein the dehydrating reagent is SOCl.sub.2, POCl.sub.3, ClCOCOCl or phosgene.

Description

DESCRIPTION OF THE METHODS AND INTERMEDIATES

EXAMPLES

[0069] The present invention is elucidated in more detail by the examples which follow, without restricting the invention to these examples.

Method of Measurement

[0070] The products were characterized by .sup.1H NMR spectroscopy and/or LC-MS (Liquid Chromatography Mass Spectrometry).

[0071] The NMR spectra were determined using a Bruker Avance 400 fitted with a flow probe head (volume 60 μl). In individual cases, the NMR spectra were measured with a Bruker Avance II 600.

Example 1

[0072] Methyl 4-aminofuran-2-carboxylate hydrochloride (salt of the formula (I)

[0073] 15.9 g (0.1 mol) of methyl 4-amino-5-hydroxy-2-oxopent-3-enoate were suspended in 50 ml of methanol and the mixture was cooled to 0° C. 17.7 g (0.15 mol) of SOCl.sub.2 were added thereto at 0° C. over 2 hours. The mixture was stirred at 10° C. for a further 5 hours and the precipitate was filtered off, washed with 5 ml of methanol and dried. This gave 16.8 g, 95% of pale beige crystals.

[0074] .sup.1H-NMR (400 MHz, CDCl.sub.3): δ 10.07 (3H, s, br.); 8.10 (1H, d); 7.32 (1H, d); 3.83 (3H, s) ppm.

[0075] .sup.13C-NMR 158.0 (s); 143.6 (s); 140.2 (d); 121.8 (s); 114.5 (d); 52.3 (q) ppm.

Example 2

[0076] Conversion of methyl 4-aminofuran-2-carboxylate hydrochloride (salt of the formula (I)) to methyl 4-aminofuran-2-carboxylate (salt-free product of the formula (I))

[0077] 9.2 g of methyl 4-aminofuran-2-carboxylate hydrochloride were suspended in 50 ml of ethyl acetate and 15.7 g of Et.sub.3N were added. The mixture was stirred at RT for 3 hours, the precipitate was filtered off and ethyl acetate fully concentrated under vacuum. This gave 6.96 g, 95% of beige crystals, with m.p. 79-81° C.

[0078] .sup.1H-NMR (400 MHz, CDCl.sub.3): δ: 7.24 (1H, d); 6.8 (1H, d); 4.3 (2H, s) 3.75 (3H, s) ppm.

Example 3

Methyl 4-[(2,2,2-trifluoroacetyl)amino]furan-2-carboxylate

[0079] 1.59 g (0.01 mol) of methyl 4-amino-5-hydroxy-2-oxopent-3-enoate were suspended in 50 ml of dichloromethane and the mixture was cooled to 0° C. 2 ml of (CF.sub.3CO).sub.2O were added thereto at 0° C. over 2 hours. The mixture was stirred at 10° C. for a further 5 hours and 20 ml of water were added. The mixture was stirred for 5 h at room temperature (RT) and then the phases were separated. The organic phase was concentrated. The precipitate was stirred with 5 ml of diisopropyl ether and filtered off. This gave 1 mg of the product as a beige solid.

[0080] .sup.1H-NMR (400 MHz, CDCl.sub.3): δ 11.76 (1H, s, br.); 8.26 (1H, d); 7.24 (1H, d); 3.76 (3H, s) ppm.

[0081] .sup.13C-NMR 158.2 (s); 154.1 (s, q); 142.5 (s); 137.4 (d); 124.7 (s); 115.8 (s); 112.1 (d); 52.3 (q) ppm.