Water → 1-Methyl-4-[3-(trifluoromethyl)phenyl]piperidin-4-ol

HRID 1980095Notes

Reaction equation

HRID 1980095 reaction equation
C([Li])CCC.Br[C:7]1[CH:8]=[C:9]([C:13]([F:16])([F:15])[F:14])[CH:10]=[CH:11][CH:12]=1.[CH3:17][N:18]1[CH2:23][CH2:22][C:21](=[O:24])[CH2:20][CH2:19]1.O>CCCCCC.O1CCCC1.C(Cl)Cl>[CH3:17][N:18]1[CH2:23][CH2:22][C:21]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([F:16])([F:15])[F:14])[CH:8]=2)([OH:24])[CH2:20][CH2:19]1

Participants

8

Reactant 4

HCID 962WaterHCID 9817Benzene, 1-bromo-3-(trifluoromethyl)-HCID 740491-Methyl-4-piperidoneHCID 178418339Butyllithium

Product 1

HCID 133633991-Methyl-4-[3-(trifluoromethyl)phenyl]piperidin-4-ol

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

A 1.5M solution of n-butyllithium in hexane (150 mL) was added under nitrogen at -70° to a stirred solution of 50 mg of 3-bromobenzotrifluoride in 300 mL of tetrahydrofuran. The mixture was stirred at -70° for 15 min and then allowed to warm to -20°. A solution of 30 g of freshly distilled 1-methyl-4-piperidone in 50 mL of tetrahydrofuran was added slowly, keeping the temperature at -20°. The mixture was then stirred at 0° for 0.5 h, and at room temperature for 3 h. Water and methylene chloride were added and the aqueous layer was extracted several times with methylene chloride. Removal of the solvent from the combined and dried methylene chloride solutions, and short-path distillation of the residue (110°-130° bath temp., 5×10-4 mm Hg [0.07 Pa]) gave 41.6 g of 1-methyl-4-(3'-trifluoromethylphenyl)-4 -piperidinol (I: R1 =Me; R2, R3 =H; R4 =m-trifluoromethylphenyl) as a solid.

Workup

  1. temperatureto warm to -20°
  2. customat -20°
  3. stirringThe mixture was then stirred at 0° for 0.5 h
  4. waitat room temperature for 3 h
  5. extractionthe aqueous layer was extracted several times with methylene chloride
  6. customRemoval of the solvent from the
  7. distillationdried methylene chloride solutions, and short-path distillation of the residue (110°-130° bath temp., 5×10-4 mm Hg [0.07 Pa])

Sources & evidence

ORD record
ord-764ae84257674263af5246429dafcc57
Source dataset
uspto-grants-1984_11
Patent number
US04485109

Reaction notes

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