Hydrochloric Acid → Ethyl 4,5,6,7-Tetrahydroisoindole-1-carboxylate

Participants

Reaction Steps

1,8-Diazabicyclo[5.4.0]-undec-7-ene (6.2 mL, 41.5 mmol) in 2-propanol (45 mL) was added addition funnel over 25 minutes to a stirring solution of 1-nitrocyclohexene (5.0441 g, 39.67 mmol) and ethylisocyanoacetate (4.3340 g, 37.16 mmol) in THF (45 mL). The reaction was judged complete after stirring overnight at room temperature. 2N HCl (˜100 mL) and EtOAc (˜50 mL) were added. The organic layer was removed, then washed with H2O, 5% NaHCO3, and H2O. The crude product was dried with Na2SO4, filtered, concentrated, and purified by silica gel chromatography (Combiflash column, 100% CH2Cl2) to obtain 171 contaminated with a minor impurity. Attempts to recrystallize from hexanes were unsuccessful at removing the impurity, so the product was carried on to the next step with no further purification. 1H (CDCl3, 400 MHz): δ 9.01 (1H, broad s), 6.64 (1H, s), 4.31 (3H, q, J=7.2 Hz), 2.82 (2H, t, J=5.6 Hz), 2.55 (2H, t, J=5.6 Hz), 1.80-1.68 (4H, m), 1.36 (3H, t, J=7.2 Hz) ppm. 13C (CD3OD, 100 MHz): δ 161.71, 128.06 and 127.84, 121.98 and 121.96, 118.74 and 118.55, 118.03 and 117.71, 59.62, 23.41 and 23.39, 23.36 and 23.33, 23.16 and 23.13, 21.88 and 21.86, 14.48ppm. DEPT (CD3OD, 100 MHz): CH3 carbons: 14.48; CH2 carbons: 59.62, 23.41 and 23.39, 23.36 and 23.33, 23.16 and 23.13, 21.88 and 21.86; CH carbons: 118.74 and 118.55 ppm. HPLC: 10.689 min.

Provenance & Evidence