Water → (+/-)-Cis-1-methyl-3-ethoxymethyl-4-(3,4-dichlorophenyl)-piperidine

HRID 227572Notes

Reaction equation

HRID 227572 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][C@H:5]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[C:10]([Cl:15])[CH:9]=2)[C@H:4]([CH2:16][OH:17])[CH2:3]1.[H-].[Na+].S(OCC)(O[CH2:24][CH3:25])(=O)=O.O>O1CCCC1>[CH3:1][N:2]1[CH2:7][CH2:6][C@H:5]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[C:10]([Cl:15])[CH:9]=2)[C@H:4]([CH2:16][O:17][CH2:24][CH3:25])[CH2:3]1

Participants

6

Reactant 4

HCID 962WaterHCID 6163Diethyl SulfateHCID 24758Sodium hydrideHCID 9860329HCID 9860329, compound

Product 1

HCID 68533369(+/-)-Cis-1-methyl-3-ethoxymethyl-4-(3,4-dichlorophenyl)-piperidineYield 57.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (3) (2.4 g, 8.6 mmol) in tetrahydrofuran (40 ml) was added 60% NaH (0.69 g, 17 mmol) and stirred at room temperature for one hour. Diethyl sulfate (1.4 ml, 11 mmol) was added and the reaction mixture stirred over night. Water was added and the reaction mixture was extracted with diethyl ether (3×40 ml). The combined organic phases was dried with magnesium sulfate and evaporated to dryness. Column chromatography, using a mixture of dichloromethane, methanol and ammonia (aq) (9:1:1%) yielded 1.5 g (56%) of product (9) (oil).

Workup

  1. stirringthe reaction mixture stirred over night
  2. extractionthe reaction mixture was extracted with diethyl ether (3×40 ml)
  3. dry with materialThe combined organic phases was dried with magnesium sulfate
  4. customevaporated to dryness
  5. additiona mixture of dichloromethane, methanol and ammonia (aq) (9:1:1%)

Sources & evidence

ORD record
ord-d6d0aab6cd984e3f857bdfc63383b306
Source dataset
uspto-grants-2009_07
Patent number
US07560562B2

Reaction notes

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