4-Toluenesulfonyl chloride → (R)-N-(2-(3,3-Diphenyl-1-propyloxy)ethyl)-3-piperidinecarboxylic acid ethyl ester

HRID 1614796Notes

Reaction equation

HRID 1614796 reaction equation
[C:1]1([CH:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:8][CH2:9][O:10][CH2:11][CH2:12]O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Li])CCC.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+].[NH:42]1[CH2:47][CH2:46][CH2:45][C@@H:44]([C:48]([O:50][CH2:51][CH3:52])=[O:49])[CH2:43]1>C1COCC1.O>[CH2:51]([O:50][C:48]([C@@H:44]1[CH2:45][CH2:46][CH2:47][N:42]([CH2:12][CH2:11][O:10][CH2:9][CH2:8][CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:43]1)=[O:49])[CH3:52]

Participants

8

Reactant 5

HCID 73974-Toluenesulfonyl chlorideHCID 11430Potassium CarbonateHCID 185582ethyl (3R)-piperidine-3-carboxylateHCID 106348432-(3,3-Diphenyl-1-propyloxy)ethanolHCID 178418339Butyllithium

Product 1

HCID 10668415(R)-N-(2-(3,3-Diphenyl-1-propyloxy)ethyl)-3-piperidinecarboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-(3,3-diphenyl-1-propyloxy)ethanol (2.5 g, 0.010 mol) in dry THF (20 ml) was placed on an ice-bath and a solution of n-butyllithium in hexanes (4.0 ml, 2.5 M) was added dropwise under an atmosphere of nitrogen. When addition was complete the reaction mixture was stirred at room temperature for 0.5 h and then heated at reflux temperature for 1 h. The mixture was cooled to room temperature and p-toluenesulphonyl chloride (2.1 g, 0.011 mol) was added. The mixture was stirred at room temperature for 0.5 h and then heated at reflux temperature for 1 h. To the cooled reaction mixture was added dry potassium carbonate (2.0 g, 0.015 mol) and ethyl (R)-3-piperidinecarboxylate (2.0 g, 0.0125 mol) and the mixture was heated at reflux temperature for 3 h. The cooled reaction mixture was poured into water (200 ml) and extracted with ethyl acetate (2×200 ml). The combined organic extracts was dried over sodium sulphate and the solvent evaporated in vacuo. The residue was submitted to flash chromatography on silica gel (150 g) using a mixture of n-heptane and THF (4:1) as eluent. This provided 0.9 g (11% calculated from 3,3-diphenyl-1-propanol) of the title compound as an oil. TLC: rf=0.24 (SiO2 ; n-heptane/THF=7:3). 1H NMR δ (CDCl3) 4.10 (t, 1H).

Workup

  1. additionWhen addition
  2. temperatureheated
  3. temperatureat reflux temperature for 1 h
  4. temperatureThe mixture was cooled to room temperature
  5. stirringThe mixture was stirred at room temperature for 0.5 h
  6. temperatureheated
  7. temperatureat reflux temperature for 1 h
  8. customTo the cooled reaction mixture
  9. temperaturethe mixture was heated
  10. temperatureat reflux temperature for 3 h
  11. customThe cooled reaction mixture
  12. extractionextracted with ethyl acetate (2×200 ml)
  13. dry with materialThe combined organic extracts was dried over sodium sulphate
  14. customthe solvent evaporated in vacuo
  15. additiona mixture of n-heptane and THF (4:1) as eluent

Sources & evidence

ORD record
ord-c9b7bbca36e7440cb3d03c0e5c7a72e6
Source dataset
uspto-grants-1993_03
Patent number
US05198451

Reaction notes

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