4-Toluenesulfonyl chloride → HCID 53691289, compound

HRID 1614800Notes

Reaction equation

HRID 1614800 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)[CH2:9][CH2:10][O:11][CH2:12][CH2:13]O)=[CH:4][CH:3]=1.C([Li])CCC.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.[NH:38]1[CH2:43][CH2:42][CH2:41][C@@H:40]([C:44]([O:46][CH2:47][CH3:48])=[O:45])[CH2:39]1.C(=O)([O-])[O-].[K+].[K+]>C1COCC1>[CH2:47]([O:46][C:44]([C@@H:40]1[CH2:41][CH2:42][CH2:43][N:38]([CH2:13][CH2:12][O:11][CH2:10][CH2:9][CH:8]([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)[C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)[CH2:39]1)=[O:45])[CH3:48]

Participants

7

Reactant 5

HCID 73974-Toluenesulfonyl chlorideHCID 11430Potassium CarbonateHCID 185582ethyl (3R)-piperidine-3-carboxylateHCID 21266410HCID 21266410, compoundHCID 178418339Butyllithium

Product 1

HCID 53691289HCID 53691289, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
10 °C

Procedure

A solution of 2-(3,3-bis(4-chlorophenyl)-1-propyloxy) ethanol (3.5 g, 10.8 mmol) in dry THF (25 ml) kept under a nitrogen atmosphere was cooled to 10° C. and a solution of n-butyllithium in hexanes (4.3 ml, 2.5 M) was added dropwise. When addition was complete the reaction mixture was stirred for 1 h at room temperature. p-Toluenesulphonyl chloride (2.1 g, 10.8 mmol) was added and the mixture was stirred at room temperature for 1.5 h. The solvent was evaporated in vacuo and acetone (30 ml) was added to the residue. The mixture was filtered and to the filtrate was added ethyl (R)-3-piperidinecarboxylate (1.8 g, 11.5 mmol) and potassium carbonate (1.5 g, 10.8 mmol). The mixture was heated at reflux temperature for 3 h and then stirred for 2 days at room temperature. The reaction mixture was filtered and the solvent was evaporated in vacuo. Flash chromatography of the residue on silica gel (200 g) using a mixture of n-heptane and ethyl acetate (6:4) as eluent provided 2.0 g (40%) of the title compound as an oil. TLC: rf=0.17 (SiO2 ; n-heptane/ethyl acetate=7.3). 1H NMR (CDCl3)δ 4.13 (t, 1H).

Workup

  1. additionWhen addition
  2. stirringthe mixture was stirred at room temperature for 1.5 h
  3. customThe solvent was evaporated in vacuo and acetone (30 ml)
  4. additionwas added to the residue
  5. filtrationThe mixture was filtered and to the filtrate
  6. temperatureThe mixture was heated
  7. temperatureat reflux temperature for 3 h
  8. stirringstirred for 2 days at room temperature
  9. filtrationThe reaction mixture was filtered
  10. customthe solvent was evaporated in vacuo
  11. additiona mixture of n-heptane and ethyl acetate (6:4) as eluent

Sources & evidence

ORD record
ord-bf0d9be44cdc414dbf51d74fb9350f4b
Source dataset
uspto-grants-1993_03
Patent number
US05198451

Reaction notes

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