Benzene, 1-bromo-2-(trifluoromethyl)- → tert-Butyl 4-hydroxy-4-[2-(trifluoromethyl)phenyl]piperidine-1-carboxylate

HRID 1044574Notes

Reaction equation

HRID 1044574 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]([F:11])([F:10])[F:9].C([Li])CCC.[O:17]=[C:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]1>C1COCC1.CCCCCC>[OH:17][C:18]1([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[C:8]([F:11])([F:10])[F:9])[CH2:19][CH2:20][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:22][CH2:23]1

Participants

6

Reactant 3

HCID 9806Benzene, 1-bromo-2-(trifluoromethyl)-HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 49760255tert-Butyl 4-hydroxy-4-[2-(trifluoromethyl)phenyl]piperidine-1-carboxylateYield 45.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

To a solution of 1-bromo-2-(trifluoromethyl)benzene (1.18 g, 5.24 mmol) in THF (20 mL) cooled at −78° C. was dropwise added a 1.60 M solution of n-butyllithium in hexane (3.4 mL). After being stirred for 40 min; a solution of tert-butyl 4-oxo-1-piperidinecarboxylate (1.0 g, 5.0 mmol) in THF (3 mL) was added and the solution stirred for 1 h at −78° C. The reaction was quenched with saturated ammonium chloride. The resulting solution was extracted with methylene chloride three times. The combined extracts were dried (MgSO4), filtered, and concentrated to give 0.78 g of a white solid which was used for the next reaction without purification. MS calculated for C17H22F3NO3: (M+H) 346; found 246.0 (M-Boc+1).

Workup

  1. stirringthe solution stirred for 1 h at −78° C
  2. customThe reaction was quenched with saturated ammonium chloride
  3. extractionThe resulting solution was extracted with methylene chloride three times
  4. dry with materialThe combined extracts were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-8b2b78d72df3408b88ae59300675c946
Source dataset
uspto-grants-2013_10
Patent number
US08563582B2

Reaction notes

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