2-((4-Chlorophenoxy)methyl)oxirane → 1-(4-Chloro-phenoxy)-3-[3-(4-trifluoromethyl-phenoxymethyl)-piperidin-1-yl]-propan-2-ol

HRID 720053Notes

Reaction equation

HRID 720053 reaction equation
[Cl:1][C:2]1[CH:12]=[CH:11][C:5]([O:6][CH2:7][CH:8]2[CH2:10][O:9]2)=[CH:4][CH:3]=1.[F:13][C:14]([F:30])([F:29])[C:15]1[CH:28]=[CH:27][C:18]([O:19][CH2:20][CH:21]2[CH2:26][CH2:25][CH2:24][NH:23][CH2:22]2)=[CH:17][CH:16]=1>CO>[Cl:1][C:2]1[CH:12]=[CH:11][C:5]([O:6][CH2:7][CH:8]([OH:9])[CH2:10][N:23]2[CH2:24][CH2:25][CH2:26][CH:21]([CH2:20][O:19][C:18]3[CH:27]=[CH:28][C:15]([C:14]([F:13])([F:29])[F:30])=[CH:16][CH:17]=3)[CH2:22]2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 915152-((4-Chlorophenoxy)methyl)oxiraneHCID 219019513-(4-Trifluoromethyl-phenoxymethyl)-piperidine

Product 1

HCID 219019401-(4-Chloro-phenoxy)-3-[3-(4-trifluoromethyl-phenoxymethyl)-piperidin-1-yl]-propan-2-olYield 79.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

2-(4-Chloro-phenoxymethyl)-oxirane (50 mg) and of 3-(4-Trifluoromethyl-phenoxymethyl)-piperidine (70 mg, 1.0 equivalent) in 4 mL of methanol were heated in a sealed tube at 100° C. for 16 hours, cooled to room temperature, transferred to a round-bottomed flask, and concentrated in vacuo. The crude residue was purified by flash chromatography on silica gel using as eluent a gradient of ethyl acetate in hexane containing 1% ammonium hydroxide. 95 mg of 1-(4-Chloro-phenoxy)-3-[3-(4-trifluoromethyl-phenoxymethyl)-piperidin-1-yl]-propan-2-ol was obtained (79%). Data for this mixture of amino alcohol diastereomers: MS 444 (M++1).

Workup

  1. customtransferred to a round-bottomed flask
  2. concentrationconcentrated in vacuo
  3. customThe crude residue was purified by flash chromatography on silica gel using as eluent a gradient of ethyl acetate in hexane containing 1% ammonium hydroxide

Sources & evidence

ORD record
ord-71e972e4e3264198818e5e27deb022c1
Source dataset
uspto-grants-2006_11
Patent number
US07132551B2

Reaction notes

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