溴乙酸乙酯 → [2-(4-Bromo-2-fluoro-benzylcarbamoyl)-5-chloro-phenoxy]-acetic acid ethyl ester

HRID 457940

反应方程式

HRID 457940 反应方程式
[Br:1][C:2]1[CH:19]=[CH:18][C:5]([CH2:6][NH:7][C:8](=[O:17])[C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][C:10]=2[OH:16])=[C:4]([F:20])[CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30]>CC(C)=O>[CH2:32]([O:31][C:29](=[O:30])[CH2:28][O:16][C:10]1[CH:11]=[C:12]([Cl:15])[CH:13]=[CH:14][C:9]=1[C:8](=[O:17])[NH:7][CH2:6][C:5]1[CH:18]=[CH:19][C:2]([Br:1])=[CH:3][C:4]=1[F:20])[CH3:33]

参与物

5

反应物 3

HCID 7748溴乙酸乙酯HCID 11430碳酸钾HCID 18468196N-(4-bromo-2-fluoro-benzyl)-4-chloro-2-hydroxy-benzamide

产物 1

HCID 22093478[2-(4-Bromo-2-fluoro-benzylcarbamoyl)-5-chloro-phenoxy]-acetic acid ethyl ester收率 94%

试剂、催化剂与溶剂 1

HCID 180丙酮溶剂

反应条件

温度
50 °C

实验过程

A solution of N-(4-bromo-2-fluoro-benzyl)-4-chloro-2-hydroxy-benzamide (3.25 g, 9.06 mmol) in acetone (45 mL, 0.2 M) was treated with aq K2CO3 (2 M, 6.8 mL, 14 mmol) and ethyl bromoacetate (1.2 mL, 11 mmol). After being heated to 50° C. for 8 h, the solution was cooled to room temperature and concentrated under reduced pressure until most of the acetone was removed. The solution was acidified to pH 1–2 with 2 N HCl, diluted with ethyl acetate and washed with saturated aq NaCl. The organic layer was dried over Na2SO4, filtered and concentrated. Purification by MPLC (10–60% ethyl acetate in heptane, 23 mL/min, 70 min) gave [2-(4-bromo-2-fluoro-benzylcarbamoyl)-5-chloro-phenoxy]-acetic acid ethyl ester as a white crystalline solid (3.78 g, 94%): mp 126–127° C.; Rf 0.61 (50% ethyl acetate in heptane); 1H NMR (DMSO-d6, 300 MHz) δ 8.90 (t, J=6 Hz, 1 H), 7.82 (d, J=8.4 Hz, 1 H), 7.52–7.47 (m, 1 H), 7.39–7.31 (m, 2 H), 7.28 (d, J=1.8 Hz, 1 H), 7.14 (dd, J1=8.4 Hz, J2=1.8 Hz, 1 H), 5.00, (s, 2 H), 4.49 (d, J=6 Hz, 2 H), 4.16 (q, J=7.2 Hz, 2 H), 1.18 (t, J=6.6 Hz, 3 H). ESI-LC/MS m/z calcd for C18 H11BrClFNO4: 444.7; found 446.0 (M+1)+. Anal. calcd for C16H16BrClFNO4: C, 48.62; H, 3.63; N, 3.15; Cl, 15.95. Found C, 48.57; H, 3.63; N, 3.11; Cl, 16.00.

后处理

  1. temperaturethe solution was cooled to room temperature
  2. concentrationconcentrated under reduced pressure until most of the acetone
  3. customwas removed
  4. additiondiluted with ethyl acetate
  5. washwashed with saturated aq NaCl
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by MPLC (10–60% ethyl acetate in heptane, 23 mL/min, 70 min)

来源与证据

ORD记录
ord-813937eeb9994e2f8cacf544791d2a97
来源数据集
uspto-grants-2007_03
专利号
US07189749B2

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