Benzene, 1-(chloromethyl)-2-fluoro- → [4-(2-Fluorobenzyloxy)-1-phenylcyclohexyl]dimethylamine

HRID 1349389Notes

Reaction equation

HRID 1349389 reaction equation
[CH3:1][N:2]([CH3:16])[C:3]1([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:8][CH2:7][CH:6]([OH:9])[CH2:5][CH2:4]1.CC(C)([O-])C.[K+].[F:23][C:24]1[CH:31]=[CH:30][CH:29]=[CH:28][C:25]=1[CH2:26]Cl>CN(C)C=O>[F:23][C:24]1[CH:31]=[CH:30][CH:29]=[CH:28][C:25]=1[CH2:26][O:9][CH:6]1[CH2:7][CH2:8][C:3]([N:2]([CH3:16])[CH3:1])([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:4][CH2:5]1

Participants

5

Reactant 3

HCID 9580Benzene, 1-(chloromethyl)-2-fluoro-HCID 111487094-Dimethylamino-4-phenylcyclohexanolHCID 23665647Potassium tert-butoxide

Product 1

HCID 10172029[4-(2-Fluorobenzyloxy)-1-phenylcyclohexyl]dimethylamineYield 14.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2.75 g of 4-dimethylamino-4-phenylcyclohexanol were dissolved in 20 ml of dimethylformamide; 1.55 g of potassium tert.-butoxide were added and stirring was carried out for 45 minutes, before 2.0 g of 2-fluorobenzyl chloride were added dropwise in the course of 30 minutes. After stirring overnight, the mixture was added to 25 ml of ice-water and extracted repeatedly with ethyl acetate. The combined extracts were washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated. The resulting crude product (3.41 g) was separated on silica gel with methanol/ethyl acetate (V:V=1:1). 580 mg of [4-(2-fluoro-benzyloxy)-1-phenylcyclohexyl]dimethylamine were obtained in the form of a white solid which, as described for Example 1, was converted into 370 mg of the corresponding hydrochloride using chlorotrimethylsilane and water in 2-butanone.

Workup

  1. additionwere added dropwise in the course of 30 minutes
  2. stirringAfter stirring overnight
  3. extractionextracted repeatedly with ethyl acetate
  4. washThe combined extracts were washed with saturated sodium chloride solution
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting crude product (3.41 g) was separated on silica gel with methanol/ethyl acetate (V:V=1:1)

Sources & evidence

ORD record
ord-a4e7e62514ce4b7ab369631794fd9ce5
Source dataset
uspto-grants-2007_05
Patent number
US07211694B2

Reaction notes

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