Hydrochloric Acid → 1,1-Dimethylethyl N-[(1S)-1-(3-fluorophenyl)-3-oxopropyl]carbamate

Participants

Reaction Conditions

Reaction Steps

To a stirring solution of the methyl ester from Example 11, Step A (2.0 mmol, 594 mg) in 20 mL of dry DCM cooled to −78° C under nitrogen was added dropwise over 20 min. Diisobutylaluminum hydride (4 mmol, 4 mL of a 4 M solution in toluene). The reaction was stirred for 2 h at −78° C. after which time MeOH (4 mL) cooled to −78° C. was canulated into the reaction mixture. After 10 min. the solution was allowed to reach room temperature. DCM (30 mL) was added to the reaction, and the solution was poured into 60 mL of 2N HCl. The organic phase was collected and the aqueous phase was extracted with DCM (2×20 mL). The combined organic phase was dried with MgSO4 and concentrated under reduced pressure. The aldehyde was further purified by flash chromatography on silica gel (40 g) using a step gradient of 0% to 16% EtOAc/hexanes, increasing in 4% increments. The aldehyde eluted in 12-16% EtOAc/hexanes, affording a white waxy solid. 1H NMR (500 MHz, CDCl3): δ 9.76 (s, 1H), 7.28-7.4 (m, 1H); 7.11 (d, 1H, J=7.7 Hz); 7.04 (dd, 1H, J=9.8 Hz, 2.0 Hz), 6.96-7.02 (m, 1H), 5.25 (br s, 1H), 2.92-3.1 (2H, m), 1.45 (s, 9H). MS (ESI): m/z 250 (M+H).

Provenance & Evidence