Chloroiodomethane → tert-butyl (1S)-3-chloro-1-(3,5-difluorobenzyl)-2-oxopropylcarbamate

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Reaction Steps

ICH2Cl (3.54 g, 1.46 mL, 19.82 mmol, 1.25 equivalent) and THF (5 mL) are added to (2S)-2-[(tert-butoxycarbonyl)amino]-3-(3,5-difluorophenyl)propanoic acid methyl ester (II, EXAMPLE 1, 5 g, 15.86 mmol, 1 equivalent). The mixture is cooled to −78° and LDA (22.3 mL, 44.60 mmol, 2.25 equivalents, 2.0M) is added dropwise maintaining an internal temperature below −60°. Once the addition is complete, the contents are stirred for 30 min at −78° at which time n-butyllithium (15.3 mL, 19.82 mmol, 1.25 equivalents; 1.3M in hexanes) is added dropwise maintaining an internal temperature below about −60°. The reaction is stirred for 30 min then quenched into 0° hydrochloric acid (IN). Ethyl acetate is added and the phases are separated and the aqueous phase is extracted with ethyl acetate. The combined organic phases are washed with saturated sodium bicarbonate, dried over sodium sulfate, filtered and concentrated under reduced pressure to give the title compound, NMR (DMSO-d6) δ 7.47, 7.06-7.14, 4.78, 4.49, 3.20, 2.82 and 1.40; CMR (DMSO-d6) δ 200.87, 163.74, 161.20, 142.74, 112.80, 102.13, 79.04, 58.97, 47.72, 34.95 and 28.30.

Provenance & Evidence