Methyl 4-acetamido-3-(benzyloxy)-6-(4-chloro-2-fluoro-3-methoxyphenyl)picolinate → Methyl 4-acetamido-6-(4-chloro-2-fluoro-3-methoxyphenyl)-3-hydroxypicolinate

HRID 407212Notes

Reaction equation

HRID 407212 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[O:25]CC1C=CC=CC=1)(=[O:3])[CH3:2]>C(O)C.[OH-].[Pd+2].[OH-]>[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]

Participants

4

Reactant 1

HCID 71150541Methyl 4-acetamido-3-(benzyloxy)-6-(4-chloro-2-fluoro-3-methoxyphenyl)picolinate

Product 1

HCID 71150438Methyl 4-acetamido-6-(4-chloro-2-fluoro-3-methoxyphenyl)-3-hydroxypicolinateYield 29%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolvent

Procedure

The methyl 4-acetamido-3-(benzyloxy)-6-(4-chloro-2-fluoro-3-methoxyphenyl)-picolinate produced in the first step was dissolved in ethyl alcohol (EtOH; 100 mL), and a catalytic amount of palladium hydroxide (Pd(OH)2) in carbon was added (2 spatula tips). The reaction mixture was stirred under a hydrogen atmosphere for 24 h, and the palladium was removed by filtration. The filtrate was concentrated, and the residue was purified by flash chromatography (SiO2; 0-50% EtOAc/hexane gradient) to provide the title compound as a white solid (0.431 g, 29% yield for the two steps): mp 168-172° C.; 1H NMR (400 MHz, CDCl3) δ 11.28 (s, 1H), 8.93 (d, J=1.6 Hz, 1H), 7.98 (s, 1H), 7.49 (dd, J=8.5, 7.6 Hz, 1H), 7.23 (dd, J=8.6, 1.8 Hz, 1H), 4.07 (s, 3H), 3.99 (d, J=1.1 Hz, 3H), 2.30 (s, 3H); ESIMS m/z 369 ([M+H]+).

Workup

  1. customthe palladium was removed by filtration
  2. concentrationThe filtrate was concentrated
  3. customthe residue was purified by flash chromatography (SiO2; 0-50% EtOAc/hexane gradient)

Sources & evidence

ORD record
ord-8389f7737cc94b93a33c3d44a55a3e6c
Source dataset
uspto-grants-2014_06
Patent number
US08754229B2

Reaction notes

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