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

HRID 2229529

반응식

HRID 2229529 반응식
[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]

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 180Acetone용매

반응 조건

온도
50 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-9f25a2161dc64fd1ae6a19dae6d75cc6
출처 데이터셋
uspto-grants-2002_07
특허 번호
US06420426B1

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