反应详情

To a stirred suspension of carbaldehyde 321 (336 mg, 0.749 mmol), (S)-1-methoxy-2-aminopropane (200 mg, 2.248 mmol) and acetic acid (68 mg, 1.124 mmol) in DCM (20 ml) at rt under nitrogen was added NaBH(OAc)3 (418 mg, 1.873 mmol). The reaction mixture was stirred at rt overnight and quenched with a solution of 10% HCl. The layers were separated; the aqueous layer was collected, washed twice with DCM and basified with 4N NaOH (pH 12) to form a suspension that was stirred for 30 min. The solid was collected by filtration, rinsed with water and air-dried and purified by flash column chromatography on silica gel (eluent 2% of ammonium hydroxyde in MeOH/DCM: 10/90) to afford the title compound 334 (182 mg, 0.35 mmol, 46% yield) as a yellow fluffy solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.71 (s, 1H), 8.58 (d, J=1.6 Hz, 1H), 8.51 (d, J=5.5 Hz, 1H), 8.31 (s, 1H), 8.23 (d, J=8.2 Hz, 1H), 7.91 (dd, J=8.2, 2.2 Hz, 1H), 7.73 (dd, J=13.6, 2.4 Hz, 1H), 7.38 (t, J=9.0 Hz, 1H), 7.23-7.17 (m, 1H), 6.64 (d, J=5.5 Hz, 1H), 6.57 (bd, J=2.7 Hz, 1H), 3.84 (d, J=14.5 Hz, 1H), 3.78 (d, J=14.5 Hz, 1H), 3.27 (dd, J=9.4, 6.3 Hz, 1H), 3.24 (s, 3H), 3.19 (dd, J=9.2, 5.5 Hz, 1H), 2.81-2.71 (m, 1H), 2.59-2.51 (m, 1H), 2.36-2.10 (m, 1H), 0.98 (d, J=6.3 Hz, 3H), 0.69-0.62 (m, 2H), 0.46-0.40 (m, 2H). MS (m/z): 522.4 (M+H).

1. customquenched with a solution of 10% HCl
2. customThe layers were separated
3. customthe aqueous layer was collected
4. washwashed twice with DCM
5. customto form a suspension that
6. stirringwas stirred for 30 min
7. filtrationThe solid was collected by filtration
8. washrinsed with water
9. customair-dried
10. custompurified by flash column chromatography on silica gel (eluent 2% of ammonium hydroxyde in MeOH/DCM: 10/90)