反应详情

A solution of (4-isopropoxy-3-methyl-phenyl)-[10-(methoxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]methanone (343 mg, 0.912 mmol) and cyclobutanone (96.0 mg, 1.36 mmol) in dichloroethane (3 mL) was treated with acetic acid (78 μL, 1.4 mmol) and stirred for 30 min. NaBH(OAc)3 (387 mg, 1.82 mmol) was added and the reaction mixture stirred for 16 h. The reaction mixture was diluted with MTBE and washed with 1N NaOH (100 mL). The organic layer was separated and washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. Silica gel chromatography (5-80% ethyl acetate/hexane) provided (4-cyclobutyl-2-(methoxymethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)(4-isopropoxy-3-methylphenyl)methanone (330 mg, 84%). ESI-MS m/z calc. 430.3. Found 431.3 (M+1)+; Retention time: 1.24 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 7.19 (d, J=8.4 Hz, 2H), 6.80 (d, J=8.1 Hz, 1H), 4.55 (hept, J=6.2 Hz, 1H), 4.30-4.10 (m, 1H), 3.94-3.75 (m, 1H), 3.62-3.46 (m, 1H), 3.48-3.33 (m, 6H), 3.30-3.16 (m, 1H), 2.75 (d, J=10.8 Hz, 1H), 2.67-2.57 (m, 1H), 2.55 (d, J=11.1 Hz, 1H), 2.47-2.27 (m, 1H), 2.20 (s, 3H), 1.98 (d, J=7.3 Hz, 2H), 1.91-1.76 (m, 1H), 1.76-1.61 (m, 4H), 1.57-1.39 (m, 3H), 1.34 (d, J=6.0 Hz, 6H).

1. stirringthe reaction mixture stirred for 16 h
2. washwashed with 1N NaOH (100 mL)
3. customThe organic layer was separated
4. washwashed with brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo