Ethyl bromoacetate → [2-(4-Bromo-2-fluoro-benzylcarbamoyl)-5-chloro-phenoxy]-acetic acid ethyl ester

HRID 2229529

反応式

HRID 2229529 の反応式
[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]

参加物

5

反応物 3

HCID 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 18468196N-(4-bromo-2-fluoro-benzyl)-4-chloro-2-hydroxy-benzamide

生成物 1

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

試薬・触媒・溶媒 1

HCID 180Acetone溶媒

反応条件

温度
50 °C

実験手順

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, 1H), 7.82 (d, J=8.4 Hz, 1H), 7.52-7.47 (m, 1H), 7.39-7.31 (m, 2H),. 7.28 (d, J=1.8 Hz, 1H), 7.14 (dd, J=8.4 Hz, J2=1.8 Hz, 1H), 5.00, (s, 2H), 4.49 (d, J=6 Hz, 2H), 4.16 (q, J=7.2 Hz, 2H), 1.18 (t, J=6.6 Hz, 3H). ESI-LC/MS ml/z calcd for C18H16BrClFNO4: 444.7; found 446.0 (M+1)+. Anal. calcd for C18H16BrClFNO4: 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.

後処理

  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)

出典と根拠

ORDレコード
ord-9f25a2161dc64fd1ae6a19dae6d75cc6
出典データセット
uspto-grants-2002_07
特許番号
US06420426B1

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