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

HRID 1367067Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1367067
[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

Komponenten

4

Edukt 2

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

Produkt 1

HCID 669202293-amino-3-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-propionic acid methyl ester HCl saltAusbeute 90,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-0fc8bd946d4b45dc89f090e76e9bddc3
Quelldatensatz
uspto-grants-2011_02
Patentnummer
US07893102B2

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