Tetrahydrofuran → 2-(3,5-Bis-trifluoromethyl-phenyl)-N-(6'-chloro-2-methyl-[3,4]bipyridinyl-3'-yl)-N-methyl-isobutyramide

HRID 547790Notes

Reaction equation

HRID 547790 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([NH:8][CH3:9])=[C:4]([C:10]2[C:11]([CH3:16])=[N:12][CH:13]=[CH:14][CH:15]=2)[CH:3]=1.O1CCCC1.C([Li])CCC.[F:27][C:28]([F:46])([F:45])[C:29]1[CH:30]=[C:31]([C:39]([CH3:44])([CH3:43])[C:40](Cl)=[O:41])[CH:32]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:34]=1>>[F:38][C:35]([F:36])([F:37])[C:33]1[CH:32]=[C:31]([C:39]([CH3:43])([CH3:44])[C:40]([N:8]([C:5]2[CH:6]=[N:7][C:2]([Cl:1])=[CH:3][C:4]=2[C:10]2[C:11]([CH3:16])=[N:12][CH:13]=[CH:14][CH:15]=2)[CH3:9])=[O:41])[CH:30]=[C:29]([C:28]([F:45])([F:27])[F:46])[CH:34]=1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 112671412-(3,5-Bis(trifluoromethyl)phenyl)-2-methylpropanoyl chlorideHCID 586946066'-Chloro-N,2-dimethyl-[3,4'-bipyridin]-3'-amineHCID 178418339Butyllithium

Product 1

HCID 210836352-(3,5-Bis-trifluoromethyl-phenyl)-N-(6'-chloro-2-methyl-[3,4]bipyridinyl-3'-yl)-N-methyl-isobutyramideYield 78.2%

Conditions

Temperature
-78 °C

Procedure

To a solution of 2.77 g (11.9 mmol) (6′-chloro-2-methyl-[3,4′]bipyridinyl-3′-yl)-methyl-amine in 120 ml tetrahydrofuran 7.8 ml (12 mmol) of a 1.6 M solution of n-butyllithium in hexanes was added dropwise at −78° C. After 30 min. 4.2 g (13 mmol) 2-(3,5-bis-trifluoromethyl-phenyl)-2-methyl-propionyl chloride were added. The reaction mixture was stirred at −78° C. for 5 min. and allowed to warm to room temperature during a period of 1 h. Dilution with 2 M aqueous sodium carbonate solution was followed by extraction with three portions of tert-butyl methyl ether. The combined organic layers were washed with 2 M aqueous sodium carbonate solution and brine, dried over sodium sulfate and concentrated in vacuo. Flash column chromatography gave 4.8 g (78%) of the title compound as an off-white solid.

Workup

  1. temperatureto warm to room temperature during a period of 1 h
  2. extractionDilution with 2 M aqueous sodium carbonate solution was followed by extraction with three portions of tert-butyl methyl ether
  3. washThe combined organic layers were washed with 2 M aqueous sodium carbonate solution and brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-92e8485bbeba424dba85573f299521dd
Source dataset
uspto-grants-2011_05
Patent number
US07939533B2

Reaction notes

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