Water → HCID 70543710, compound

HRID 1389857Notes

Reaction equation

HRID 1389857 reaction equation
[OH:1][C@H:2]1[C@H:7]([O:8][C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[C:11]([CH3:16])[CH:10]=2)[CH2:6][CH2:5][N:4]([C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[CH2:3]1.[H-].[Na+].[Cl:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32](F)[CH:31]=1.O>CN(C)C=O>[Cl:29][C:30]1[CH:31]=[C:32]([CH:33]=[CH:34][CH:35]=1)[O:1][C@H:2]1[C@H:7]([O:8][C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[C:11]([CH3:16])[CH:10]=2)[CH2:6][CH2:5][N:4]([C:17]([O:19][CH2:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)=[O:18])[CH2:3]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 2230871-Chloro-3-fluorobenzeneHCID 13186890HCID 13186890, compound

Product 1

HCID 70543710HCID 70543710, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 15.0 g (0.04 mol) of the trans-3-hydroxy-4-(3,4-dimethyl-phenoxy)-1-carbobenzyloxy-piperidine described in Example 19 in 100 ml of dimethylformamide is introduced in the course of 30 minutes, at 30°-35°, into a suspension of 2.8 g (0.062 mol) of a 55% strength oily dispersion of sodium hydride in 50 ml of dimethylformamide. The mixture is then warmed to 50° and treated dropwise with 7.16 g (0.055 mol) of 1-chloro-3-fluorobenzene. The reaction mixture is subsequently stirred for 41/2 hours at 60°-70° and then for 15 hours at room temperature, cooled in an ice-water bath and treated with 250 ml of water. The mixture is extracted by shaking with 3 times 250 ml of ethyl acetate and the combined organic phases are washed twice with water, dried over magnesium sulphate and evaporated to dryness, first under a water pump vacuum and then under a high vacuum. The oil which remains behind is dissolved in 100 ml of toluene and the solution is filtered through a layer of silica gel. Elution with a toluene/ethyl acetate mixture (4:1) gives trans-3-(3-chloro-phenoxy)-4-(3,4-dimethylphenoxy)-1-carbobenzyloxy-piperidine in the form of a pale yellow oil.

Workup

  1. temperatureThe mixture is then warmed to 50°
  2. waitfor 15 hours at room temperature
  3. temperaturecooled in an ice-water bath
  4. extractionThe mixture is extracted
  5. stirringby shaking with 3 times 250 ml of ethyl acetate
  6. washthe combined organic phases are washed twice with water
  7. dry with materialdried over magnesium sulphate
  8. customevaporated to dryness, first under a water pump vacuum
  9. dissolutionThe oil which remains behind is dissolved in 100 ml of toluene
  10. filtrationthe solution is filtered through a layer of silica gel
  11. washElution with a toluene/ethyl acetate mixture (4:1)

Sources & evidence

ORD record
ord-39e441ce69434fec95c68f2940935f4e
Source dataset
uspto-grants-1981_01
Patent number
US04246269

Reaction notes

Loading…