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

HRID 346889Notes

Reaction equation

[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

Participants

Conditions

Temperature: 0 °C

Procedure

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).

Workup

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

Sources & evidence

ORD record: ord-9797b2cade4943cda3266814eba9c3a3
Source dataset: uspto-grants-2007_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07173058B2

Reaction notes

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