Ammonia → ((1S,2S,4S)-2-Hydroxy-4-hydroxymethyl-1-{(S)-2-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-3-methyl-butyl}-5-methyl-hexyl)-carbamic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of 1 g of the pyrrolidine 8 in 17 mL of THF is cooled to −78° C. and 17 mL of ammonia condensed into the flask. To the mixture is added 0.44 g of Sodium and the resulting dark-coloured mixture stirred over night at −78° C. To the mixture is added 2.6 g of ammonium chloride. The mixture is allowed to warm to r.t. (ammonia evaporates off and unreacted sodium is dissolved) before addition of 40 mL of toluene and 1.9 g of acetic acid. After 10 min 25 mL of water is added and the phases are separated. The aqueous phase is back-extracted with 25 mL of toluene, then the combined organic phases are washed four times with 1:1 water-brine before drying over sodium sulfate and evaporating in vacuum. Purification of the crude oily product (0.86 g) on silica gel, eluting with ethyl acetate-heptane affords e.g. 0.71 g of pure 9a. 1H-NMR (CDCl3, 300K): 6.8 (2H), 6.7 (1H), 4.7 (1H), 4.1 (2H), 3.8 (3H), 3.5-3.7 (5H), 3.4-3.5 (1H), 3.4 (3H), 2.7-2.8 (1H), 2.4-2.5 (3H), 2.0-2.2 (2H), 1.5-1.8 (8H), 1.4 (9H), 0.8-0.9 (12H).

Provenance & Evidence