Sodium Hydroxide → (8R)-5,6,7,8-Tetrahydroquinolin-8-amine

Participants

Reaction Steps

A stirred solution of (R)-(−)-N-(5,6,7,8-tetrahydroquinolin-8-yl)-acetamide (230 mg, 1.21 mmol, 97% ee) in 6 N aqueous HCl (4.0 mL) was heated to 130° C. for 2 h. At this time, the reaction mixture was cooled to room temperature and cautiously rendered basic with a minimum amount of saturated aqueous NaOH, then diluted with CH2Cl2 (10 mL). The phases were separated and the aqueous phase was washed with CH2Cl2 (5×20 mL), then the combined organic phases were dried (MgSO4) and concentrated. Flash chromatography through a plug of silica gel (elution with 20:2:1 CH2Cl2—MeOH—NH4OH) afforded 143 mg (80%) of (R)-(−)-8-amino-5,6,7,8-tetrahydroquinoline in 96% ee (separated by chiral GC, J&W CycloSil B column, initial temperature: 160° C., initial time: 0 min, rate: 1° C./min, final temperature: 130° C., final time: 0 min, (S)-(+)-enantiomerrt=12.43 min, (R)-(−)-enantiomerrt=13.13 min). [α]D=−125.7 (c 0.56, CHCl3); 1H NMR (CDCl3) δ 1.52–1.62 (m, 2H), 1.78–1.85 (m, 1H), 1.91 (br s, 2H), 2.02–2.06 (m, 1H), 2.60–2.65 (m, 2H), 3.83–3.87 (m, 2H), 6.91 (dd, 1H, J=8, 5 Hz), 7.21 (dd, 1H, J=8, 1 Hz), 8.26 (d, 1H, J=5 Hz); 13C NMR (CDCl3) δ 19.6, 28.7, 31.7, 51.0, 121.3, 131.2, 136.4, 146.7, 159.2. ES-MS m/z 149 (M+H).

Provenance & Evidence