Oxygen → (3R,4R)-1-(tert-Butoxycarbonyl)-4-(4-fluorophenyl)piperidine-3-carboxylic acid

Participants

Reaction Steps

In a glove box (O2 content≦2 ppm) a 35 ml autoclave equipped with a 15 ml glass insert and a magnetic stirring bar was charged with 4-(4-fluoro-phenyl)-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid-1-tert-butyl ester (0.300 g, 0.934 mmol), [Ru(OAc)2((S)-3,5-Xyl-4-MeO)-MeOBIPHEP] (9.67 mg, 0.00936 mmol), triethylamine (15 mg, 0.16 mmol, 0.16 eq.) and 5 ml of methanol. The asymmetric hydrogenation was run for 42 h at 80° C. under 40 bar of hydrogen. After cooling to room temperature the pressure was released from the autoclave, the methanol solution was diluted with 50 ml of tert-butyl methyl ether and extracted with two 50-ml portions of a 1 M aqueous sodium hydroxide solution. The aqueous layer was poured on ice, acidified with ice-cold 2 M aqueous hydrochloric acid solution to pH 1 and extracted with two 100-ml portions of ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to give (+)-(3R,4R)-4-(4-fluoro-phenyl)-piperidine-1,3-dicarboxylic acid-1-tert-butyl ester in 89% yield (0.27 g) and with 96.6% ee.

Provenance & Evidence