Methanol → N-(3,5-bis-trifluoromethyl-benzyl)-N-methyl-6-piperazin-1-yl-4-o-tolyl-nicotinamide

HRID 1017458Notes

Reaction equation

HRID 1017458 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[C:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[CH3:26])[C:17]([C:27](=[O:45])[N:28]([CH2:30][C:31]3[CH:36]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:34]=[C:33]([C:41]([F:44])([F:43])[F:42])[CH:32]=3)[CH3:29])=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.CO.[OH-].[Na+]>C(OCC)(=O)C>[F:43][C:41]([F:42])([F:44])[C:33]1[CH:32]=[C:31]([CH:36]=[C:35]([C:37]([F:39])([F:40])[F:38])[CH:34]=1)[CH2:30][N:28]([CH3:29])[C:27](=[O:45])[C:17]1[C:18]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[CH3:26])=[CH:19][C:14]([N:11]2[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)=[N:15][CH:16]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 98523194-{5-[(3,5-Bis-trifluoromethyl-benzyl)-methyl-carbamoyl]-4-o-tolyl-pyridin-2-yl}-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 10280286N-(3,5-bis-trifluoromethyl-benzyl)-N-methyl-6-piperazin-1-yl-4-o-tolyl-nicotinamideYield 87.4%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of 6.60 g (104 mmol) 4-{5-[(3,5-bis-trifluoromethyl-benzyl)-methyl-carbamoyl]-4-o-tolyl-pyridin-2-yl}-piperazine-1-carboxylic acid tert-butyl ester (Example 43) and 8.40 ml (207 mmol) methanol in 50 ml ethyl acetate 14.7 ml (207 mmol) acetyl chloride were added dropwise at 0° C. After 4 h the reaction mixture was diluted with ethyl acetate and treated with 1 N sodium hydroxide solution. The layers were separated and the aqueous layer extracted with dichloromethane. The combined organic layers were dried with sodium sulfate and concentrated to give 5.36 g of crude product. Flash column chromatography afforded 4.86 g (87.4%) of the title compound as a light brown solid.

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer extracted with dichloromethane
  3. dry with materialThe combined organic layers were dried with sodium sulfate
  4. concentrationconcentrated
  5. customto give 5.36 g of crude product

Sources & evidence

ORD record
ord-e77bd9115f424472a531ad67dc32fc4a
Source dataset
uspto-grants-2002_11
Patent number
US06479483B2

Reaction notes

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