Ethyl Acetate → 1-t-Butoxycarbonyl-3-{2-[4-(3-methoxyphenyl)butyl]phenoxymethyl}piperidine

HRID 743327Notes

Reaction equation

HRID 743327 reaction equation
CC(C)([O-])C.[K+].[CH3:7][O:8][C:9]1[CH:10]=[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[OH:25])[CH:12]=[CH:13][CH:14]=1.[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][CH2:36][CH:35]([CH2:39]OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:34]1)=[O:32])([CH3:29])([CH3:28])[CH3:27].C(OCC)(=O)C>CC(N(C)C)=O.O>[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][CH2:36][CH:35]([CH2:39][O:25][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[CH2:18][CH2:17][CH2:16][CH2:15][C:11]2[CH:12]=[CH:13][CH:14]=[C:9]([O:8][CH3:7])[CH:10]=2)[CH2:34]1)=[O:32])([CH3:29])([CH3:27])[CH3:28]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 108010802-[4-(3-Methoxyphenyl)butyl]phenolHCID 18369320Tert-butyl 3-((P-tolylsulfonyloxy)methyl)piperidine-1-carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 106473391-t-Butoxycarbonyl-3-{2-[4-(3-methoxyphenyl)butyl]phenoxymethyl}piperidineYield 150.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent2×

Procedure

0.965 g of potassium t-butoxide was added to a solution of 1.70 g of 2-[4-(3-methoxyphenyl)butyl]phenol (prepared as described in Preparation 7) in 30 ml of dimethylacetamide, whilst ice-cooling, and the mixture was stirred at the same temperature for 15 minutes. A solution of 3.18 g of 1-t-butoxycarbonyl-3-(p-toluenesulfonyloxymethyl)piperidine in 30 ml of dimethylacetamide was then added dropwise to the solution at the same temperature, and the mixture was stirred at 55° C. for 1.5 hours. At the end of this time, the reaction mixture was cooled, and 200 ml of ethyl acetate and 100 ml of water were added to the mixture, which was then shaken. The ethyl acetate layer was separated, washed twice with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate. The ethyl acetate layer was then concentrated by distillation under reduced pressure, and the concentrate was purified by column chromatography through silica gel, using a 3:1 by volume mixture of hexane and ethyl acetate as the eluent, to give 4.54 g (yield 95%) of the title compound as a colorless oil.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred at 55° C. for 1.5 hours
  3. temperatureAt the end of this time, the reaction mixture was cooled
  4. stirringwas then shaken
  5. customThe ethyl acetate layer was separated
  6. washwashed twice with a saturated aqueous solution of sodium chloride
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationThe ethyl acetate layer was then concentrated by distillation under reduced pressure
  9. customthe concentrate was purified by column chromatography through silica gel
  10. additionby volume mixture of hexane and ethyl acetate as the eluent

Sources & evidence

ORD record
ord-346dffede40b4122a0188115567195b4
Source dataset
uspto-grants-1996_09
Patent number
US05556864

Reaction notes

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