Sodium borohydride → tert-Butyl ((2S,4R)-1-azido-7-chloro-4-(hydroxymethyl)heptan-2-yl)carbamate

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Reaction Conditions

Reaction Steps

The (3R,5S)-tert-butyl 5-(azidomethyl)-3-(3-chloropropyl)-2-oxopyrrolidine-1-carboxylate (10.11 g, 31.9 mmol, 10. equiv) was dissolved in 200 mL of MeOH. Solid NaBH4 was added in ˜1 g portions at a rate to maintain the reaction temperature at ˜27° C. Subsequent portions of NaBH4 were added only after the previous charge had completely dissolved. After the addition of ˜3 g of NaBH4 (˜80 mmol, 2.5 equiv) over a 3 h period, LC/MS analysis showed >95% conversion to the desired alcohol. The residual hydride reagent was quenched by cooling the mixture to 0° C. and carefully adding 1.0 M HCl until H2 evolution ceased. The methanol was removed in vacuo and the mixture diluted with ˜200 mL of EtOAc. The mixture was transferred to a separatory funnel and the layers separated. The aqueous layer was extracted with additional EtOAc and the combined organic layers washed with brine, dried over Na2SO4, filtered through a pad of silica and evaporated. This yielded ˜10 g of tert-butyl (2S,4R)-1-azido-7-chloro-4-(hydroxymethyl)heptan-2-ylcarbamate which possessed sufficient purity to employ in the subsequent step with no further purification.

Provenance & Evidence