Acetyl chloride → 3-amino-3-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-propionic acid methyl ester HCl salt

HRID 346889노트

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HRID 346889 반응식
[NH2:1][CH:2]([C:7]1[CH:12]=[CH:11][C:10]([O:13][CH:14]([F:16])[F:15])=[C:9]([O:17][CH2:18][CH:19]2[CH2:21][CH2:20]2)[CH:8]=1)[CH2:3][C:4]([OH:6])=[O:5].[C:22]([Cl:25])(=O)C>CO>[ClH:25].[CH3:22][O:5][C:4](=[O:6])[CH2:3][CH:2]([NH2:1])[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH:14]([F:16])[F:15])=[C:9]([O:17][CH2:18][CH:19]2[CH2:21][CH2:20]2)[CH:8]=1

참가 물질

4

반응물 2

HCID 6367Acetyl chlorideHCID 210823383-Amino-3-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-propionic acid

생성물 1

HCID 669202293-amino-3-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-propionic acid methyl ester HCl salt수율 90.3%

시약·촉매·용매 1

HCID 887Methanol용매

반응 조건

온도
0 °C

실험 절차

To a stirred suspension of 3-amino-3-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-propionic acid (500 mg, 1.7 mmol) in methanol (10 ml) was added dropwise acetyl chloride (0.3 ml, 4.3 mmol) under nitrogen atmosphere at 0° C. After the addition, the mixture was stirred at 0° C. for 15 min and the ice bath was removed. The mixture was stirred at room temperature overnight. Solvent was removed in vacuo. The resulted solid was stirred with ether (30 ml) for 2 hours. The suspension was filtered to give 3-amino-3-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-propionic acid methyl ester HCl salt as a white solid (540 mg, 90%). 1HNMR (DMSO-d6): δ 0.30–0.36 (m, 2H), 0.54–0.61 (m, 2H), 1.22–1.32 (m, 1H), 3.01–3.10 (m, 1H), 3.56 (s, 3H), 3.89 (d, J=7.5 Hz, 2H), 4.53–4.63 (m, 1H), 7.04 (d, J=7.5 Hz, 1H), 7.09 (t, JH-F=75 Hz, 1H), 7.19 (d, J=7.5 Hz, 1H), 7.39 (s, 1H), 8.55 (broad, 3H).

후처리

  1. additionAfter the addition
  2. customthe ice bath was removed
  3. stirringThe mixture was stirred at room temperature overnight
  4. customSolvent was removed in vacuo
  5. stirringThe resulted solid was stirred with ether (30 ml) for 2 hours
  6. filtrationThe suspension was filtered

출처 및 근거

ORD 기록
ord-9797b2cade4943cda3266814eba9c3a3
출처 데이터셋
uspto-grants-2007_02
특허 번호
US07173058B2

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