Cesium fluoride → 4-Acetylamino-3-chloro-6-(4-chloro-2-fluoro-5-methoxyphenyl)pyridine-2-carboxylic acid methyl ester

HRID 1782615

Reaction equation

HRID 1782615 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:10]([Cl:11])=[C:9]([NH:12][C:13](=[O:15])[CH3:14])[CH:8]=[C:7](Cl)[N:6]=1)=[O:4].[Cl:17][C:18]1[C:23]([O:24][CH3:25])=[CH:22][C:21](B2OCCCO2)=[C:20]([F:32])[CH:19]=1.[F-].[Cs+].C1(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:1][O:2][C:3]([C:5]1[C:10]([Cl:11])=[C:9]([NH:12][C:13](=[O:15])[CH3:14])[CH:8]=[C:7]([C:21]2[CH:22]=[C:23]([O:24][CH3:25])[C:18]([Cl:17])=[CH:19][C:20]=2[F:32])[N:6]=1)=[O:4]

Participants

8

Reactant 4

HCID 25953Cesium fluorideHCID 821241,4-Bis(diphenylphosphino)butaneHCID 22677481Methyl 4-acetamido-3,6-dichloropyridine-2-carboxylateHCID 669547012-(4-Chloro-2-fluoro-5-methoxyphenyl)-[1,3,2]-dioxaborinane

Product 1

HCID 686005934-Acetylamino-3-chloro-6-(4-chloro-2-fluoro-5-methoxyphenyl)pyridine-2-carboxylic acid methyl esterYield 75%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A solution of 4-acetylamino-3,6-dichloropyridine carboxylic acid methyl ester (4.3 g, 0.016 mol), 2-(4-chloro-2-fluoro-5-methoxyphenyl)-[1,3,2]-dioxaborinane (4.5 g, 0.018 mol), cesium fluoride (3.5 g, 0.025 mol), and 1,4-bis(diphenylphosphino)butane (0.360 g, 0.0016 mol) in acetonitrile (100 mL) was degassed with nitrogen for 15 minutes before palladium acetate (0.180 g, 0.0016 mol) was added and the solution heated under reflux for 18 hours. Water (150 mL) was added and the resulting solid collected and dried to give 4-acetylamino-3-chloro-6-(4-chloro-2-fluoro-5-methoxyphenyl)pyridine-2-carboxylic acid methyl ester (4.5 g, 0.012 mol): mp 180-182° C.

Workup

  1. additionwas added
  2. temperaturethe solution heated
  3. temperatureunder reflux for 18 hours
  4. customthe resulting solid collected
  5. customdried

Sources & evidence

ORD record
ord-9d5521e78560442b906e15943c2ba77c
Source dataset
uspto-grants-2009_03
Patent number
US07498468B2

Linked notes

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