Dimethylformamide → HCID 18790138, compound

Participants

Reaction Steps

To a solution containing (-)-2-(2-benzenesulfonylethyl)-3-(3,4-dimethoxyphenylsulfanyl)-7-phenylheptanoic acid (285 mg, 0.53 mmol) in anhydrous CH2Cl2 (10 mL) under nitrogen atmosphere is added anhydrous DMF (41 μL, 0.53 mmol) followed by oxalyl chloride (2 M in CH2Cl2, 0.66 mL, 1.31 mmol). The yellow solution is stirred for 30 minutes then O-(trimethylsilyl)hydroxylamine (0.32 mL, 2.65 mmol) is added dropwise. The resulting white precipitate is stirred for 10 minutes then partitioned between 1 N HCl (50 mL) and ethyl acetate (50 mL). The aqueous layer is extracted with ethyl acetate (2×20 mL) and the combined organic extracts are washed with water (30 mL), brine (30 mL), dried over anhydrous MgSO4, filtered and concentrated to afford a pale yellow oil. The crude product is combined with the product of a reaction performed on identical scale and chromatographed on silica gel (CH2Cl2 →CH2Cl2 :MeOH, 19:1) to afford (-)-N-hydroxy-2-(2-benzenesulfonylethyl)-3-(3,4-dimethoxyphenylsulfanyl)-7-phenylheptanamide (560 mg, 95%) as a cream-colored foam. TLC analysis [pet-ether/EtOAc, 1:2, Rf (carboxylic acid)=0.45, Rf (hydroxamate)=0.40]. [α]23D -28° (c 1.1, CHCl3); 1H NMR (300 MHz, CDCl3) δ 1.40-1.80 (m, 6H), 2.10 (m, 1H), 2.22 (m, 1H), 2.60 (m, 2H), 2.68 (m, 1H), 3.05 (broad s, 3H), 3.83 (s, 3H), 3.84 (s, 3H), 6.76 (d, J=8.7 Hz, 1H), 6.98 (m, 2H), 7.12 (m, 3H), 7.28 (m, 2H), 7.52 (m, 2H), 7.64 (t, J=7.3 Hz, 1H), 7.84 (d, J=7.4 Hz, 2H), 8.85 (broad s, 1H) ppm. Mass spectrum (FAB) m/z 557 (M)+.

Provenance & Evidence