反应详情

A solution of tert-butyl 10-(hydroxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (3.10 g, 10.8 mmol), 2-chloropyrimidine (1.86 g, 16.2 mmol) and sodium carbonate (2.30 g, 21.7 mmol) in DMSO (15 mL) was heated at 110° C. for 1 h. The reaction mixture was diluted with ethyl acetate (200 mL), washed with water (4×100 mL), dried over Na2SO4, and concentrated in vacuo. Silica gel column chromatography (0-60% ethyl acetate/hexane) provided tert-butyl 10-(hydroxymethyl)-8-pyrimidin-2-yl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (3.18 g, 8.73 mmol, 80%). ESI-MS m/z calc. 364.2. Found 365.3 (M+1)+; Retention time: 1.21 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 8.29 (d, J=4.7 Hz, 2H), 6.50 (t, J=4.7 Hz, 1H), 4.64 (ddd, J=16.0, 8.5, 1.5 Hz, 2H), 3.90-3.80 (m, 1H), 3.79-3.56 (m, 4H), 3.44-3.22 (m, 1H), 3.13 (t, J=10.6 Hz, 1H), 2.90-2.71 (m, 2H), 2.19 (d, J=8.9 Hz, 1H), 1.98 (dd, J=10.6, 3.6 Hz, 1H), 1.69-1.58 (m, 2H), 1.45 (s, 9H).

1. washwashed with water (4×100 mL)
2. dry with materialdried over Na2SO4
3. concentrationconcentrated in vacuo