Sodium Hydroxide → HCID 11444904, compound

HRID 1951685Notes

Reaction equation

HRID 1951685 reaction equation
[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([C:13]([CH3:34])([CH3:33])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21](Cl)=[CH:22][C:23]=2[C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=2[CH3:31])[CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C([SiH2][O:42][C:43](C)(C)[C@@H:44]1[CH2:49][O:48][CH2:47][CH2:46][NH:45]1)(C)(C)C.[OH-].[Na+]>[Br-].C([N+](C)(C)C)CCCCCCCCCCCCCCC.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.C1(C)C=CC=CC=1>[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([C:13]([CH3:34])([CH3:33])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21]([N:45]3[CH2:46][CH2:47][O:48][CH2:49][C@H:44]3[CH2:43][OH:42])=[CH:22][C:23]=2[C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=2[CH3:31])[CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 235027842-(3,5-Bis(trifluoromethyl)phenyl)-N-(6-chloro-4-(4-fluoro-2-methylphenyl)pyrid-3-yl)-N,2-dimethylpropanamideHCID 131728826HCID 131728826, compound

Product 1

HCID 11444904HCID 11444904, compoundYield 30%

Reagents, catalysts & solvents 3

HCID 5974Hexadecyltrimethylammonium BromideCatalystHCID 178418851HCID 178418851, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 0.30 g (0.56 mmol) 2-(3,5-bis-trifluoromethyl-phenyl)-N-[6-chloro-4-(4-fluoro-2-methyl-phenyl)-pyridin-3-yl]-N-methyl-isobutyramide, 0.17 g (0.73 mmol) (S)-3-(tert-butyl-dimethyl-silanyloxymethyl)-morpholine, 0.01 g (0.03 mmol) cetyltrimethylammonium bromide, 0.029 g (0.056 mmol) bis(tri-t-butylphosphine)palladium(0), 0.07 ml NaOH 50% and 3 ml toluene was degassed by two freeze-thaw cycles. The reaction mixture was heated under argon at 90° C. for 3 h. After cooling to room temperature the mixture was diluted with water and extracted with three portions of toluene. The combined organic layers were dried over sodium sulphate and concentrated in vacuo. The residue was dissolved in a mixture of 10 ml methanol and 0.5 ml concentrated aqueous hydrochloric acid solution. After stirring at room temperature for 90 min. the reaction mixture was neutralized with 0.5 M aqueous sodium hydroxide solution and extracted with three portions of tert-butyl methyl ether. The combined organic layers were dried over sodium sulfate and concentrated in vacuo. Flash column chromatography gave 0.10 g (30%) of the title compound as an off-white solid.

Workup

  1. customwas degassed by two freeze-thaw cycles
  2. temperatureAfter cooling to room temperature the mixture
  3. additionwas diluted with water
  4. extractionextracted with three portions of toluene
  5. dry with materialThe combined organic layers were dried over sodium sulphate
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in a mixture of 10 ml methanol and 0.5 ml concentrated aqueous hydrochloric acid solution
  8. extractionextracted with three portions of tert-butyl methyl ether
  9. dry with materialThe combined organic layers were dried over sodium sulfate
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3c9f071d62f141eb8be03eb71dd1672b
Source dataset
uspto-grants-2013_03
Patent number
US08404708B2

Reaction notes

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