Phenol → (S)-4-benzyl-2-(2-phenoxyethyl)piperazine-1-carboxylic acid tert-butyl ester

HRID 131401Notes

Reaction equation

HRID 131401 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10][C@@H:9]1[CH2:21][CH2:22][O:23]S(C)(=O)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[I-].[Na+].[C:30]1(O)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>CN(C)C=O.C(=O)(O)[O-].[Na+]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10][C@@H:9]1[CH2:21][CH2:22][O:23][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 996PhenolHCID 5238Sodium IodideHCID 86604576(S)-4-benzyl-2-(2-methanesulfonyloxy-ethyl)piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 69215534(S)-4-benzyl-2-(2-phenoxyethyl)piperazine-1-carboxylic acid tert-butyl esterYield 25%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Combine (S)-4-benzyl-2-(2-methanesulfonyloxyethyl)piperazine-1-carboxylic acid tert-butyl ester (2.82 g, 7.08 mmol), sodium iodide (0.106 g, 0.708 mmol), and phenol (3.33 g, 35.4 mmol) in dimethyl formamide (40 mL) and stir at 100° C. for 20 hours. Dilute the mixture with saturated aqueous sodium bicarbonate and extract three times with dichloromethane. Combine the organic layers, dry over sodium sulfate and concentrate under reduced pressure. Purify by flash chromatography, eluting with a step gradient (100% dichloromethane to 5% 2N ammonia-methanol in dichloromethane) to obtain (S)-4-benzyl-2-(2-phenoxyethyl)piperazine-1-carboxylic acid tert-butyl ester (0.703 g, 25%): mass spectrum (APCI): m/z=397.2 (M+1).

Workup

  1. extractionextract three times with dichloromethane
  2. dry with materialdry over sodium sulfate
  3. concentrationconcentrate under reduced pressure
  4. customPurify by flash chromatography
  5. washeluting with a step gradient (100% dichloromethane to 5% 2N ammonia-methanol in dichloromethane)

Sources & evidence

ORD record
ord-9910739c1c9941daa5f8519c0335ad00
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Reaction notes

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