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

HRID 1349394Notes

Reaction equation

HRID 1349394 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 36.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2.00 g of 4-dimethylamino-4-phenylcyclohexanol were dissolved in 20 ml of dimethylformamide; 1.13 g of potassium tert.-butoxide were added and stirring was carried out for 45 minutes, before 1.45 g of 2-fluorobenzyl chloride were added dropwise in the course of 15 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 (2.61 g) was separated on silica gel with hexane/diethyl ether (V:V=1:1). 1.08 g of [4-(2-fluorobenzyloxy)-1-phenylcyclohexyl]dimethylamine were obtained and, as described for Example 1, were converted into 970 mg of the corresponding hydrochloride using chlorotrimethylsilane and water in 2-butanone.

Workup

  1. additionwere added dropwise in the course of 15 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 (2.61 g) was separated on silica gel with hexane/diethyl ether (V:V=1:1)

Sources & evidence

ORD record
ord-af7bf36da71d4286b1e1922931ba2fae
Source dataset
uspto-grants-2007_05
Patent number
US07211694B2

Reaction notes

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