反应详情

温度

-20 °C

To a solution of N-isopropylpropan-2-amine (0.57 mL, 4.1 mmol) in THF (3.5 mL) was added a solution of n-butyllithium in hexane (2.6 mL of 1.6 M, 4.1 mmol) dropwise at −78° C. under Ar. The solution was allowed to stir at −20° C. for 15 min and then cooled to −78° C. tert-Butyl 4-oxospiro[chromane-2,4′-piperidine]-1′-carboxylate (1.1 g, 3.5 mmol) in THF (3.5 mL) was added at −78° C. followed by the addition of acetaldehyde (0.22 mL, 3.9 mmol) in THF (3 mL). The reaction was quenched with saturated aqueous ammonium chloride at −78° C., warmed to 25° C. and extracted with ethyl acatate (2×). The combined organic layers were washed with brine, dried over MgSO4 and concentrated to dryness. Purification by silica gel chromatography (20-30% ethyl acetate in hexane) provided tert-butyl 3-(1-hydroxyethyl)-4-oxospiro[chroman-2,4′-piperidine]-1′-carboxylate (0.80 g, 63%) as a colorless oil. ESI-MS m/z calc. 361.2, found 362.5 (M+1)+; Retention time: 1.79 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 7.87 (dd, J=7.8, 1.6 Hz, 1H), 7.55-7.48 (m, 1H), 7.06-6.96 (m, 2H), 4.33-4.23 (m, 1H), 4.10-3.93 (m, 1H), 3.88-3.67 (m, 1H), 3.41-3.27 (m, 1H), 3.07-2.94 (m, 1H), 2.62 (d, J=5.2 Hz, 1H), 2.45 (d, J=8.5 Hz, 1H), 2.20-2.00 (m, 2H), 1.85-1.76 (m, 1H), 1.58-1.49 (m, 1H), 1.46 (s, 9H), 1.26 (t, J=7.1 Hz, 1H) 1.13 (d, J=6.6 Hz, 3H).

1. additionwas added at −78° C.
2. customThe reaction was quenched with saturated aqueous ammonium chloride at −78° C.
3. temperaturewarmed to 25° C.
4. extractionextracted with ethyl acatate (2×)
5. washThe combined organic layers were washed with brine
6. dry with materialdried over MgSO4
7. concentrationconcentrated to dryness
8. customPurification by silica gel chromatography (20-30% ethyl acetate in hexane)