1-Benzyl-4-piperidone → 1-Benzyl-4-[4-chloro-3-(trifluoromethyl)phenyl]-4-piperidinol

HRID 2232930Notes

Reaction equation

HRID 2232930 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:12])=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[CH2:13]([N:20]1[CH2:25][CH2:24][C:23](=[O:26])[CH2:22][CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C(OCC)C>[CH2:13]([N:20]1[CH2:25][CH2:24][C:23]([C:2]2[CH:3]=[CH:4][C:5]([Cl:12])=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=2)([OH:26])[CH2:22][CH2:21]1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

4

Reactant 2

HCID 192201-Benzyl-4-piperidoneHCID 679594-Bromo-2-chloro-alpha,alpha,alpha-trifluorotoluene

Product 1

HCID 223451801-Benzyl-4-[4-chloro-3-(trifluoromethyl)phenyl]-4-piperidinolYield 64%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent3×

Procedure

A solution of 5-Bromo-2-chlorobenzotrifluoride (5 g, 19.2 mmol) in dry diethyl ether (40 ml) was added dropwise at room temperature to a mixture of Mg (470 mg) in dry diethyl ether (20 ml) under a stream of Argon (g). The reaction gave rise to a solution of Grignard's reagent. A solution of 1-benzyl-4-piperidone (1.3 g, 6.88 mmol) in dry diethyl ether (30 ml) was added dropwise via syringe at room temperature. The combined mixture was stirred for 1 hour, and finally quenched with saturated ammonium chloride solution (40 ml). The mixture was extracted several times with EtOAc and the combined organic phases were dried (MgSO4), filtered and evaporated to dryness. The oily residue was chromathographed on a silica column using EtOAc:toluene (1:1 (v/v)) as eluent affording the title compound (1.6 g, 64%). MS m/z (relative intensity, 70 eV) 369 (M+, 23), 278 (15), 91 (bp), 65 (16), 56 (21).

Workup

  1. customThe reaction gave rise to a solution of Grignard's reagent
  2. customfinally quenched with saturated ammonium chloride solution (40 ml)
  3. extractionThe mixture was extracted several times with EtOAc
  4. dry with materialthe combined organic phases were dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated to dryness

Sources & evidence

ORD record
ord-25e77246674f4f29b03a7d9940ce5b9e
Source dataset
uspto-grants-2010_05
Patent number
USRE041315E1

Reaction notes

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