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

HRID 743373
Notes
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Reaction equation

HRID 743373 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]([CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[OH:19])[CH:8]=[CH:9][CH:10]=1.[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][CH2:30][C@H:29]([CH2:33]OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21].C(OCC)(=O)C>CC(N(C)C)=O.O>[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][CH2:30][C@H:29]([CH2:33][O:19][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[CH2:12][CH2:11][C:7]2[CH:8]=[CH:9][CH:10]=[C:5]([O:4][CH3:3])[CH:6]=2)[CH2:28]1)=[O:26])([CH3:23])([CH3:21])[CH3:22]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 105854482-(2-(3-Methoxyphenyl)ethyl)phenolHCID 45158786tert-Butyl (3S)-3-{[(4-methylbenzene-1-sulfonyl)oxy]methyl}piperidine-1-carboxylate

Product 1

HCID 53797160(S)-1-t-Butoxycarbonyl-3-{2-[2-(3-methoxyphenyl) ethyl]phenoxymethyl}piperidineYield 96.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

0.295 g of a 50% w/w dispersion of sodium hydride in mineral oil was added to a solution of 1.55 g of 2-[2-(3-methoxyphenyl)ethyl]phenol (prepared as described in Preparation 21) in 60 ml of dimethylacetamide, whilst ice-cooling and stirring, and the mixture was stirred at the same temperature for 15 minutes. 2.50 g of (S)-1-t-butoxycarbonyl-3-(p-toluenesulfonyloxymethyl)piperidine were then added to the mixture, whilst ice-cooling, and the mixture was stirred at the same temperature for 30 minutes and then at room temperature for 6 hours. At the end of this time, 250 ml of ethyl acetate and 150 ml of water were added to the reaction mixture, and the ethyl acetate layer was separated. The aqueous layer was extracted with 50 ml of ethyl acetate once, and the ethyl acetate layer and the extract were combined, washed with a saturated aqueous solution of sodium chloride twice, dried over anhydrous magnesium sulfate and concentrated by distillation under reduced pressure. The concentrate was purified by column chromatography through silica gel, using a 5:1 by volume mixture of hexane and ethyl acetate as the eluent, to give 2.78 g (yield 96%) of the title compound as a colorless oil.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred at the same temperature for 15 minutes
  3. temperaturecooling
  4. stirringthe mixture was stirred at the same temperature for 30 minutes
  5. customthe ethyl acetate layer was separated
  6. extractionThe aqueous layer was extracted with 50 ml of ethyl acetate once
  7. washwashed with a saturated aqueous solution of sodium chloride twice
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated by distillation under reduced pressure
  10. customThe concentrate was purified by column chromatography through silica gel
  11. additionby volume mixture of hexane and ethyl acetate as the eluent

Sources & evidence

ORD record
ord-eebb613ac410412794b1ee66b188c4da
Source dataset
uspto-grants-1996_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05556864

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes