methyl 3-amino-4-fluorobut-2-enoate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (S)-2,2,2-Trichloro-1-phenylethyl 2-(2,3-dichlorophenylmethylene)-3-oxobutanoate (10.8 g, 23 mmoles) and methyl 3-amino-4-fluoro-2-butenoate (3.7 g, 28 mmoles) were heated at 55° in dry tert-butanol (50 ml) for 68 hours. The solvent was removed and the residue purified and separated into single diastereomers by HPLC eluting with methylene chloride/petroleum ether (60°-80° ) mixtures. The solvent was removed the residue purified separated into single diastereomers by HPLC eluting with methylene chloride/petroleum ether (60°-80° ) mixtures

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of the product of step (a) (2.9 g, 7.6 mmoles) and methyl 3-amino-4-fluoro-2-butenoate (1 g, 7.6 mmoles) in dry tert-butanol (20 ml) was heated to 60° (oil bath temperature) for 16 hours. The solution was allowed to cool to room temperature and the solvent removed in vacuo. Chromatography on silica, eluting with dichloromethane/ethyl acetate mixtures afforded the title compound as an oil which crystallised on addition of petroleum ether (60°-80° ). The solid was recrystallised from petroleum ether (60°-80° )/acetone to afford the title compound 1.03 g, mp 155°-6°. the solvent removed in vacuo Chromatography on silica, eluting with dichloromethane/ethyl acetate mixtures

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The product of step (a) (1.7 g, 5.4 mmoles) and methyl 3-amino-4-fluoro-2-butenoate (0.72 g, 5.4 mmoles) were mixed and heated to 95° (oil bath temperature) under an atmosphere of nitrogen for 6 hours. The oil was allowed to cool to room temperature. Chromatography on silica eluting with petroleum ether (60°-80° )/ethyl acetate mixtures, afforded the title compound as a yellow solid, which was recrystallised from petroleum ether (60°-80° ) to afford the title compound 0.37 g, mp 148°-9°. heated to 95° (oil bath temperature) under an atmosphere of nitrogen for 6 hours

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of the product of step (a) (5.1 g, 14.3 mmoles) and methyl 3-amino-4-fluoro-2-butenoate (1.9 g, 14.3 mmoles) in dry tert-butanol (25 ml) was heated to 60° (oil bath temperature) for 108 hours. The solution was allowed to cool to room temperature and the solvent removed in vacuo. Chromatography on silica eluting with dichloromethane afforded the title compound as a yellow oil which crystallises on addition of petroleum ether (60°-80° ) to afford the title compound 1.5 g mp 148°-9°. (Identical with the product of Example 3). the solvent removed in vacuo