4-Nitrobenzoic Acid → Di-tert-butyl (1S,2R,3S,4S,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-[(3,4-dichlorobenzyl)oxy]-4-{[(4-nitrophenyl)carbonyl]oxy}bicyclo[3.1.0]hexane-2,6-dicarboxylate

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Reaction Steps

Triphenylphosphine (12.66 g, 48.26 mmol) and 4-nitrobenzoic acid (8.19 g, 48.26 mmol) are added to di-tert-butyl (1S,2R,3S,4R,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-[(3,4-dichlorobenzyl)oxy]-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylate (14.20 g, 24.13 mmol) and tetrahydrofuran (241.28 mL, 2.97 moles) at room temperature. Cool the mixture in an ice bath. Diisopropyl azodicarboxylate (9.57 mL, 9.76 g, 48.26 mmol) in tetrahydrofuran (20 mL) is added and the reaction mixture is gradually warmed to room temperature overnight. Dilute with diethyl ether, and then wash with aqueous sodium carbonate. Extract the aqueous layer again with diethyl ether. Combine all ether extracts, wash with water, brine, dry over magnesium sulfate, and concentrate under reduced pressure to give a residue. The residue is purified by flash chromatography, eluting with 10-100% ethyl acetate in hexanes to give the title compound (9 g, 12.2 mmol, 51%): MS (m/z): 759 (M+1).

Provenance & Evidence