反应详情

Titanium(IV) isopropoxide (0.20 mL, 0.68 mmol) was added to a methanol solution of methylamine (0.75 mL 2M, 1.50 mmol). The resulting solution was added to 53C (162 mg, 0.45 mmol) and then methanol (1 mL) was added. After 60 min, DCM (5 mL) was added and the solution was stirred for 2 h. Sodium borohydride (21 mg, 0.56 mmol) was added and the mixture was stirred for 60 min. Water was added and the mixture was filtered through Celite and the solid was washed extensively with DCM. The filtrate was further filtered through a phase separator and the organic solution was evaporated. The product was purified by preparative HPLC (Kromasil, C8) eluting with a gradient of acetonitrile and a mixture of acetic acid and water (0.2%). The pure fractions were combined and freeze-dried twice. There was obtained 74 mg (44%) of 53 as a solid. 1NMR (500 MHz, CDCl3): δ 2.27 (s, 3H), 2.3-2.6 (m, 4H), 3.62 (m, 2H), 4.24 (dd, 1H), 4.56 (dd, 1H), 4.66 (dd, 1H), 4.99 (m, 1H), 5.04 (m, 1H), 6.49 (d, 1H), 6.54 (s, 1H), 7.15 (d, 1H), 7.46 (t, 2H), 7.51 (t, 1H), 8.08 (d, 2H), MS (APCI+) m/z 379 [M+H]+, LC purity: 99%.

1. stirringthe mixture was stirred for 60 min
2. filtrationthe mixture was filtered through Celite
3. washthe solid was washed extensively with DCM
4. filtrationThe filtrate was further filtered through a phase separator
5. customthe organic solution was evaporated
6. customThe product was purified by preparative HPLC (Kromasil, C8)
7. washeluting with a gradient of acetonitrile
8. additiona mixture of acetic acid and water (0.2%)
9. customfreeze-dried twice