2,2-difluoro-N-(2-hydroxyethyl)propanamide

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

Procedure: To a stirred solution of lithium aluminum hydride (5.5 g, 146 mmol) in diethyl ether (85 ml) was added a solution of 2,2-difluoro-N-(2-hydroxy-ethyl)-propionamide (11.2 g, 73 mmol) in diethyl ether (55 ml) dropwise at such a rate to maintain a gentle reflux. After an additional 1.5 hours, the reaction was quenched with sodium sulfate decahydrate, diluted with ethyl acetate and allowed to stir for 18 hours. The mixture was filtered with the aid of diatomaceous earth, washing with ethyl acetate. The filtrate was concentrated in vacuo and fractionally distilled (11 torr, collecting fractions distilling at 75–88° C.) to afford the title compound (I-3c) as a colorless oil, 4.5 g. to maintain a gentle reflux the reaction was quenched with sodium sulfate decahydrate diluted with ethyl acetate The mixture was filtered with the aid of diatomaceous earth washing with ethyl acetate The filtrate was concentrated in vacuo fractionally distilled (11 torr, collecting fractions distilling at 75–88° C.)

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

Procedure: 2,2-Difluoro-propionic acid ethyl ester I-3a (10.1 g, 70 mmol) was added dropwise to stirred, cooled (0° C.) ethanolamine (4.4 ml, 70 mmol) and the resulting solution was allowed to stir at ambient temperature for 4 hours. Concentration of the reaction mixture in vacuo afforded the title compound (I-3b) as a solid, 11.2 g. to stir at ambient temperature for 4 hours

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

Procedure: 2,2-Difluoro-propionic acid ethyl ester I-3a (10.1 g, 70 mmol) was added dropwise to stirred, cooled (0° C.) ethanolamine (4.4 ml, 70 mmol) and the resulting solution was allowed to stir at ambient temperature for 4 hours. Concentration of the reaction mixture in vacuo afforded the title compound (I-3b) as a solid, 11.2 g. to stir at ambient temperature for 4 hours

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

Procedure: To a stirred solution of lithium aluminum hydride (5.5 g, 146 mmol) in diethyl ether (85 ml) was added a solution of 2,2-difluoro-N-(2-hydroxy-ethyl)-propionamide (11.2 g, 73 mmol) in diethyl ether (55 ml) dropwise at such a rate to maintain a gentle reflux. After an additional 1.5 hours, the reaction was quenched with sodium sulfate decahydrate, diluted with ethyl acetate and allowed to stir for 18 hours. The mixture was filtered with the aid of diatomaceous earth, washing with ethyl acetate. The filtrate was concentrated in vacuo and fractionally distilled (11 torr, collecting fractions distilling at 75–88° C.) to afford the title compound (I-3c) as a colorless oil, 4.5 g. to maintain a gentle reflux the reaction was quenched with sodium sulfate decahydrate diluted with ethyl acetate The mixture was filtered with the aid of diatomaceous earth washing with ethyl acetate The filtrate was concentrated in vacuo fractionally distilled (11 torr, collecting fractions distilling at 75–88° C.)

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

Procedure: 2,2-Difluoro-propionic acid ethyl ester I-3a (10.1 g, 70 mmol) was added dropwise to stirred, cooled (0° C.) ethanolamine (4.4 ml, 70 mmol) and the resulting solution was allowed to stir at ambient temperature for 4 hours. Concentration of the reaction mixture in vacuo afforded the title compound (I-3b) as a solid, 11.2 g. to stir at ambient temperature for 4 hours