正己烷 → (S)-4-benzyl-3-(3-(biphenyl-4-yl)propanoyl)oxazolidin-2-one

HRID 70870

反应方程式

HRID 70870 反应方程式
[Li]CCCC.CCCCCC.[CH2:12]([C@H:19]1[CH2:23][O:22][C:21](=[O:24])[NH:20]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[C:25]1([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:30]=[CH:29][C:28]([CH2:31][CH2:32][C:33](Cl)=[O:34])=[CH:27][CH:26]=1>C1COCC1.C(=O)=O.CO>[CH2:12]([C@H:19]1[CH2:23][O:22][C:21](=[O:24])[N:20]1[C:33](=[O:34])[CH2:32][CH2:31][C:28]1[CH:29]=[CH:30][C:25]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[CH:26][CH:27]=1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

参与物

7

反应物 4

HCID 8058正己烷HCID 736225(S)-4-苄基-2-唑烷酮HCID 596075633-(Biphenyl-4-yl)propanoyl chloride2 次HCID 178418339正丁基锂

产物 1

HCID 59607884(S)-4-benzyl-3-(3-(biphenyl-4-yl)propanoyl)oxazolidin-2-one收率 60.1%

试剂、催化剂与溶剂 2

HCID 8028四氢呋喃溶剂2 次HCID 21973728Carbon dioxide methanol溶剂

反应条件

温度
-60.5 °C

实验过程

To a 1.6 M solution of n-BuLi in hexane (12.1 mL, 19.3 mmol) is added dropwise a solution of (S)-(−)-4-benzyl-2-oxazolidinone (3.26 g, 18.4 mmol) in dry THF (80 mL) at −71.6° C. under nitrogen over 10 minutes. The solution is warmed up to −60.5° C. while the addition, and allowed to stir for 1 hour in dry ice/MeOH bath. 3-(Biphenyl-4-yl)propanoyl chloride (intermediate 13: 5.46 g, 22.31 mmol) in dry THF (20 mL) is added dropwise at −72° C. over 5 minutes. The solution is warmed up to −56.5° C. while the addition. After stirring 10 minutes at the same temperature, the reaction mixture is allowed to warm to room temperature and stirring is continued for 3 hours. The reaction mixture is filtered, and the collected precipitate is washed with 20 mL (10 mL×2) of MeOH and then with 150 mL of H2O to give the desired product (4.26 g). The products in the mother liquor is extracted with ethyl acetate, washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The obtained residue is suspended in 80 mL of MeOH, and the suspension is filtered and washed with 20 mL of MeOH (1.79 g). The two fractions are mixed to give (S)-4-benzyl-3-(3-(biphenyl-4-yl)propanoyl)oxazolidin-2-one (6.05 g, 85% in 2 steps). Retention time=1.77 minutes (condition A); MS (m+1)=387.3; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.77 (dd, J=13.39, 9.35 Hz, 1 H) 2.99-3.15 (m, 2 H) 3.20-3.43 (m, 3 H) 4.09-4.24 (m, 2 H), 4.68 (dddd, J=9.76, 6.73, 3.47, 3.28 Hz, 1 H) 7.18 (d, J=7.07 Hz, 2 H) 7.23-7.37 (m, 6 H) 7.42 (t, J=7.58 Hz, 2 H) 7.53 (d, J=8.1 Hz, 2 H), 7.57 (d, J=7.8 Hz, 2 H).

后处理

  1. temperatureThe solution is warmed up to −56.5° C. while the addition
  2. temperatureto warm to room temperature
  3. stirringstirring
  4. waitis continued for 3 hours
  5. filtrationThe reaction mixture is filtered
  6. washthe collected precipitate is washed with 20 mL (10 mL×2) of MeOH

来源与证据

ORD记录
ord-cd0f914c8e53463db5d3cc833a567297
来源数据集
uspto-grants-2014_09
专利号
US08822534B2

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