Methanol → Methyl 4-acetamido-6-(4-chloro-2-fluoro-3-methoxyphenyl)-3-methoxypicolinate

HRID 407213Notes

Reaction equation

HRID 407213 reaction equation
[C:1]([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[OH:25])(=[O:3])[CH3:2].[C:26]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.CO>C1COCC1.CCOC(C)=O.C1CCCCC1>[C:1]([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:3])[CH3:2]

Participants

7

Reactant 4

HCID 887MethanolHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 71150438Methyl 4-acetamido-6-(4-chloro-2-fluoro-3-methoxyphenyl)-3-hydroxypicolinate

Product 1

HCID 71150616Methyl 4-acetamido-6-(4-chloro-2-fluoro-3-methoxyphenyl)-3-methoxypicolinateYield 43.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21867204Cyclohexane ethylacetateSolvent

Procedure

Methyl 4-acetamido-6-(4-chloro-2-fluoro-3-methoxyphenyl)-3-hydroxypicolinate (568 mg, 1.54 mmol), triphenylphosphine (404 mg, 1.54 mmol), diethyl azodicarboxylate (243 μL, 1.54 mmol), and CH3OH (94 μL, 2.31 mmol) were combined in THF and allowed to stir for 24 h. Flash chromatography (SiO2; 0-50% EtOAc/cyclohexane gradient) afforded the title compound as a yellow oil (255 mg, 43%): 1H NMR (400 MHz, CDCl3) δ 8.93 (d, J=1.6 Hz, 1H), 8.06 (s, 1H), 7.56 (dd, J=8.5, 7.7 Hz, 1H), 7.23 (dd, J=8.6, 1.7 Hz, 1H), 4.01 (s, 3H), 3.99 (d, J=1.0 Hz, 3H), 3.98 (s, 3H), 2.29 (s, 3H); ESIMS m/z 383 ([M+H]+).

Sources & evidence

ORD record
ord-b567a220ed714929a6786a13c31b6c76
Source dataset
uspto-grants-2014_06
Patent number
US08754229B2

Reaction notes

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