Acetyl chloride → Methyl 4-amino-6-(4-chloro-2-fluoro-3-methoxyphenyl)-3-methoxypicolinate

HRID 407214Notes

Reaction equation

C([NH:4][C:5]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([O:18][CH3:19])[C:12]=2[F:20])[N:8]=[C:7]([C:21]([O:23][CH3:24])=[O:22])[C:6]=1[O:25][CH3:26])(=O)C.C(Cl)(=O)C>CO>[NH2:4][C:5]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([O:18][CH3:19])[C:12]=2[F:20])[N:8]=[C:7]([C:21]([O:23][CH3:24])=[O:22])[C:6]=1[O:25][CH3:26]

Participants

Conditions

Temperature: 25 °C

Procedure

Methyl 4-acetamido-6-(4-chloro-2-fluoro-3-methoxyphenyl)-3-methoxypicolinate (209 mg, 0.55 mmol) was dissolved in CH3OH (10 mL), and acetyl chloride (194 μL, 2.73 mmol) was added dropwise to the mixture. The reaction mixture was allowed to stir at 25° C. for 3 h. Additional acetyl chloride (194 μL, 2.73 mmol) was then added, and the reaction mixture was allowed to stir at 25° C. overnight. The reaction mixture was concentrated to dryness and purified by flash chromatography (SiO2; 0-50% EtOAc/hexane gradient) to provide the title compound as an off-white solid (30 mg, 16%): mp 114-118° C.; 1H NMR (400 MHz, CDCl3) δ 7.61 (dd, J=8.5, 7.8 Hz, 1H), 7.22 (dd, J=8.6, 1.8 Hz, 1H), 7.18 (d, J=2.1 Hz, 1H), 4.54 (s, 1H), 3.98 (s, 2H), 3.96 (d, J=0.8 Hz, 2H), 3.92 (s, 2H); ESIMS m/z 341 ([M+H]+), 339 ([M−H]−).

Workup

stirringto stir at 25° C. overnight
concentrationThe reaction mixture was concentrated to dryness
custompurified by flash chromatography (SiO2; 0-50% EtOAc/hexane gradient)

Sources & evidence

ORD record: ord-097ee8e4604b4b4e9e0c94d8d6676581
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754229B2

Reaction notes

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