Methanol → HCID 22229145, compound

Participants

Reaction Steps

This example describes the preparation of I where n=3 and R1=p-fluorophenyl. In a nitrogen-filled glove box, a Fisher-Porter tube was charged with iridium catalyst prepared as in Example 1 (10 mg, 0.012 mmol) and 3-(p-fluorobenzylidene)caprolactam (250 mg, 1.1 mmol). Methanol (3 mL) and dichloromethane (3 mL) were added and the system was flushed 4 times with hydrogen and pressured to 60 psi (0.5 MPa) H2. After 18 h the reaction mixture was filtered through a short pad of silica. The solvent was removed at reduced pressure to afford 3-(p-fluorobenzyl)caprolactam (230 mg, 92%) as a white crystalline solid. Chiral HPLC analysis (Chiralpak AS, 60% heptane, 39.2% isopropanol, 0.4% trifluoroacetic acid, 0.4% n-hexylamine, 40° C.) indicated that conversion was 100% and the enantiomeric excess was 67%. 19F NMR δ −117.99; 13C NMR δ 28.93, 29.47, 29.94, 36.73, 42.28, 45.65, 115.18 (d, J=21 Hz), 130.81, 136.47, 161.49 (d, J=241 Hz), 179.79; 1H NMR: δ 1.43 (m, 3H), 1.70 (m, 1H), 1.76 (m, 1H), 1.91 (m, 1H), 2.54 (app. dd, 1H), 2.67 (m, 1H), 3.12-3.31 (m, 3H), 6.78 (br s, 1H), 6.96 (m, 2H), 7.14 (m, 2H).

Provenance & Evidence