Thionyl Chloride → tert-Butyl 4-(trifluoromethyl)-3',6'-dihydro-2,4'-bipyridine-1'(2'H)-carboxylate

HRID 270567Notes

Reaction equation

HRID 270567 reaction equation
O[C:2]1([C:15]2[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][N:16]=2)[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.S(Cl)(Cl)=O>N1C=CC=CC=1>[F:24][C:21]([F:22])([F:23])[C:19]1[CH:18]=[CH:17][N:16]=[C:15]([C:2]2[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:12])([CH3:14])[CH3:13])=[O:9])[CH2:4][CH:3]=2)[CH:20]=1

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 59833581tert-Butyl4-hydroxy-4-[4-(trifluoromethyl)pyridin-2-yl]piperidine-1-carboxylate

Product 1

HCID 59833541tert-Butyl 4-(trifluoromethyl)-3',6'-dihydro-2,4'-bipyridine-1'(2'H)-carboxylateYield 53.3%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of tert-butyl 4-hydroxy-4-[4-(trifluoromethyl)pyridin-2-yl]piperidine-1-carboxylate (2.00 g, 2.31 mmol) in pyridine (15.9 mL) cooled in an ice bath was slowly added thionyl chloride (0.84 mL, 12 mmol). The mixture was allowed to warm to room temperature and stirred overnight (17 h). The brown reaction mixture was quenched with ice water and extracted with methylene chloride three times. The combined extracts were dried (MgSO4), filtered, and concentrated. The residue was purified by flash chromatography on silica gel (0-10% B over 25 min. Bottle A=hexanes, Bottle B=EtOAc) to give 404 mg (53%) of desired product as light brown oil. LC-MS calculated for C16H19F3N2O2: (M+H) 329; found 273.1 (M-tBu+1).

Workup

  1. customThe brown reaction mixture was quenched with ice water
  2. extractionextracted with methylene chloride three times
  3. dry with materialThe combined extracts were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography on silica gel (0-10% B over 25 min

Sources & evidence

ORD record
ord-7aab953dca7643ada18d46bccbd83e28
Source dataset
uspto-grants-2008_11
Patent number
US07449467B2

Reaction notes

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