Lithium tri-s-butylborohydride → HCID 86640810, compound

Participants

Reaction Steps

To a chilled (−78° C.) solution of 2-methyl-propane-2-sulfinic acid [1-(6-bromopyridin-3-yl)-prop-(E)-ylidene]-amide (10.4 g, 32.78 mmol) in THF (150 mL) is added a 1 M solution of L-Selectride (33.0 mL, 33.0 mmol) in THF. The reaction is monitored by TLC (EtOAc-ether 3:7) indicating a single diastereomer (when compared to a mixture of diastereomers prepared by a reduction of 2-methyl-propane-2-sulfinic acid [1-(6-bromopyridin-3-yl)-prop-(E)-ylidene]-amide with lithium borohydride in THF). After 6 hours, the mixture is quenched with saturated aqueous ammonium chloride (100 mL) and extracted with EtOAc (3×100 mL). The combined organic layers are washed with saturated aqueous ammonium chloride (2×50 mL), brine (50 mL), dried over magnesium sulfate, filtered and concentrated. The crude material is purified by silica gel chromatography eluting with ether-dichloromethane (0:100, then 5:95, then 1:9, then 2:8). The material from the chromatography is triturated with ether to afford in two crops material which by 1H NMR is consistent with a single diastereomer however an impurity is present by TLC (EtOAc-ether 3:7). This material and the filtrate is purified by silica gel chromatography separately using EtOAc-dichloromethane (0:100, then 4:96, then 8:98, then 12:88, then 2:8, then 3:7, then 4:6). The material from the two purifications is combined and crystallized from dichloromethane-hexanes-ether to afford in 3 crops 2-methyl-propane-2-sulfinic acid [(S)-1-(6-bromopyridin-3-yl)-propyl]-amide.

Provenance & Evidence