Dimethyl Sulfoxide → tert-Butyl 4-formylpiperidine-1-carboxylate

Participants

Reaction Steps

A mixture of 17.62 g (135.6 mmole) oxalyl chloride and 250 mL DCM in a dry ice acetone bath was treated with a solution of 21.19 g (271.2 mmole) DMSO in 150 mL DCM over 20 minutes. After stirring for 20 minutes, a solution of 24.327 g 1-(t-butoxycarbonyl)-4-hydroxymethyl-piperidine (from Step 1 above) in 150 mL DCM was added over one hour. After an additional 15 minutes, 57.17 (565 mmole) triethylamine in 150 mL DCM was added over half an hour. The reaction mixture was allowed to warm up over night in the cooling bath. The reaction mixture was concentraed under vacuum to remove about 400 mL DCM, and the residue was partitioned between 1 L ether and 300 mL water. To this was added 200 mL 1 N NaOH, the layers were separated, and the organic layer was washed with 150 mL 1 N NaOH (2×), water (3×), and saturated brine, dried over sodium sulfate, and concentrated to give 22.562 g crude product. FC (10-60% ethyl acetate in hexanes) gave 20.58 g title compound as slightly yellowish oil. RF: 0.29 (3:1 v/v hexanes/EtOAc); 1H NMR (500 MHz) δ 9.68 (d, J=0.7 Hz, 1H), 3.96-4.02 (m, 2H), 2.92-2.97 (m, 2H), 2.40-2.45 (m, 1H), 1.88-1.94 (m, 2H), 1.53-1.64 (m, 2H), 1.47 (s, 9H).

Provenance & Evidence