3-Pyridinemethanol → HCID 15344102, compound

Participants

Reaction Conditions

Reaction Steps

In an atmosphere of nitrogen, 3-hydroxymethylpyridine (35.95 g, 0.329 mol) was dissolved in N,N-dimethylformamide (250 ml) followed by cooling to -15°~-20° C. Then, triethylamine (36.65 g, 0.329 mol) was added thereto and methanesulfonyl chloride (41.45 g, 0.362 mol) was added dropwise to the mixture at 0°~-10° C. After completion of the dropwise addition, the mixture was stirred at -10° C. for 30 minutes. To this mixture were added (2S,4R)-2-methoxycarbonyl-4-hydroxypyrrolidine hydrochloride (50 g, 0.275 mol) and triethylamine (100 g, 0.988 mol) followed by warming to 65° C. The mixture was stirred at 65° C. for 1 hour to provide a reaction mixture containing (2S,4R)-1-(3-pyridylmethyl)-2-methoxycarbonyl-4-hydroxypyrrolidine. This reaction mixture was cooled to -20° C. and triethylamine (66.8 g, 0.66 mol) was added thereto. Then, methanesulfonyl chloride (75.6 g, 0.66 mol) was added thereto dropwise at -20°~-15° C. The mixture was stirred at -20°~-25° C. for 1 hour, after which it was poured into ethyl acetate (1 l)-water (1 l) and extracted. After phase separation, the aqueous layer was extracted with ethyl acetate (500 ml) twice. The ethyl acetate layer was combined and washed with a saturated aqueous sodium chloride solution (125 ml). The ethyl acetate layer was concentrated to dryness under reduced pressure to provide (2S,4R)-1-(3-pyridylmethyl)-2-methoxycarbonyl-4-methylsulfonyloxypyrrolidine (84.65 g) as an oil.

Provenance & Evidence