反应详情
EQUATION
反应方程式
REACTANTS
反应物
PRODUCTS
生成物
AUXILIARIES
试剂、催化剂与溶剂
CONDITIONS
反应条件
- 温度
- -55 °C
PROCEDURE
实验过程
A solution of anhydrous DMSO (0.82 mL, 0.90 g, 11.5 mmol, 6.0 eg) in dry DCM (20 mL) was added dropwise to a stirred solution of oxalyl chloride (2.88 mL of a 2 M solution in DAM, 5.76 mmol, 3.0 eq) under a nitrogen atmosphere at −60° C. (liq N2/CHCl3). After stirring at −55° C. for 1.5 h, a solution of the substrate 11 (2.26 g, 1.92 mmol) in dry DCM (30 mL) was added dropwise to the reaction mixture, which was then stirred for a further 2 h at −45° C. A solution of TEA (10.8 mL, 7.82 g; 71.7 mmol, 4.2 eq) in dry DCM (90 mL) was added dropwise to the mixture and stirred for a further 30 min. The reaction mixture was left to warm to 0° C., washed with cold 1 N HCl (2×50 mL), H2O (50 mL), brine (50 mL) and dried (MgSO4). Filtration and evaporation of the solvent in vacuo afforded the crude product which was purified by flash column chromatography (70:30 v/v hexane/EtOAc then gradient to 40:60 v/v hexane/EtOAc) to afford carbinolamine 12 as a white glass (1.62 g, 72%): 1H NMR (400 MHz, CDCl3) δ 7.02 (s, 2H, H6), 6.54 (s, 2H, H9), 5.59 (d, 2H, J=9.2 Hz, H11), 4.98 (d, 2H, J=12.0 Hz, Troc CH2), 4.09-3.86 (m, 8H, OCH2CH2CH2O, Troc CH2 and H3), 3.75-3.66 (m, 10H, OCH3×2, H11a, and H3), 2.72 (dd, 2H, J=10.2, 19.6 Hz, H1), 2.82 (dd, 2H, J=2.6, 19.6 Hz, H1), 2.22-2.19 (m, 2H, OCH2CH2CH2O), 0.63 (s, 18H, TBS CH3×6), 0.00 (s×2, 12H, TBS CH3×4); 13C NMR (100.6 MHz, CDCl3) δ 207.7 (C2), 168.0 (Cquat), 153.7 (Cquat), 150.7 (Cquat), 149.4 (Cquat), 127.8 (Cquat), 124.6 (Cquat), 114.0 (C9), 110.6 (C6), 95.1 (Troc CCl3), 87.4 (C11), 74.8 (Troc CH2), 65.0 (OCH2CH2CH2O), 58.9 (C11a), 56.1 (OCH3), 53.0 (C3), 40.3 (C1), 28.8 (OCH2CH2CH2O), 25.6 (TBS CH3), 17.8 (TBS Cquat); MS (ES), m/z (relative intensity) 1224 ([M+48]+., 100), 1210 ([M+34]+., 60), 1199 ([M+Na]+., 35), 1192 ([M+16]+., 40), 1176 (M+., 18).
WORKUP
后处理
- stirringwas then stirred for a further 2 h at −45° C
- stirringstirred for a further 30 min
- waitThe reaction mixture was left
- temperatureto warm to 0° C.
- washwashed with cold 1 N HCl (2×50 mL), H2O (50 mL), brine (50 mL)
- dry with materialdried (MgSO4)
- filtrationFiltration and evaporation of the solvent in vacuo
- customafforded the crude product which
- customwas purified by flash column chromatography (70:30 v/v hexane/EtOAc