4-Toluenesulfonyl chloride → HCID 11070095, compound

HRID 2226746Notes

Reaction equation

HRID 2226746 reaction equation
O[CH2:2][CH2:3][CH2:4][O:5][CH2:6][CH:7]=[C:8]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[CH2:12][CH2:11][C:10]2[CH:19]=[CH:20][CH:21]=[CH:22][C:9]1=2.C([Li])CCC.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.[NH:39]1[CH2:44][CH2:43][CH2:42][C@@H:41]([C:45]([O:47][CH2:48][CH3:49])=[O:46])[CH2:40]1.C(=O)([O-])[O-].[K+].[K+]>C1COCC1>[CH2:48]([O:47][C:45]([C@@H:41]1[CH2:42][CH2:43][CH2:44][N:39]([CH2:2][CH2:3][CH2:4][O:5][CH2:6][CH:7]=[C:8]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[CH2:12][CH2:11][C:10]3[CH:19]=[CH:20][CH:21]=[CH:22][C:9]2=3)[CH2:40]1)=[O:46])[CH3:49]

Participants

7

Reactant 5

HCID 73974-Toluenesulfonyl chlorideHCID 11430Potassium CarbonateHCID 185582ethyl (3R)-piperidine-3-carboxylateHCID 10880940HCID 10880940, compoundHCID 178418339Butyllithium

Product 1

HCID 11070095HCID 11070095, compoundYield 48.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of the above alcohol (4.2 g, 14.3 mmol) in dry THF (30 ml) was placed under an atmosphere of nitrogen and placed on an ice-bath. A solution of n-butyllithium in hexanes (5.7 ml, 2.5 M) was added dropwise within 15 minutes and the mixture was stirred for another 15 minutes. p-Toluenesulfonyl chloride (2.7 g, 14.0 mmol) was added in one portion and the mixture was stirred at room temperature for 30 minutes. The solvent was evaporated in vacuo keeping a low bath temperature. The oily residue was dissolved in acetone (25 ml) and ethyl (R)-3-piperidinecarboxylate (3.3 g, 21.0 mmol) and potassium carbonate (3.5 g, 25.0 mmol) were added. The mixture was stirred at room temperature for 120 h. The mixture was filtered and the solvent was evaporated in vacuo. The oily residue was submitted to column chromatography on silica gel (100 g) using a mixture of ethyl acetate and n-heptane (2:3) as eluent. Collecting the proper fractions afforded 3.0 g of (R)-N-(3-(2-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)ethoxy)-1-propyl)-3-piperidinecarboxylic acid ethyl ester as an oil. TLC: rf=0.19 (SIC2 ; ethyl acetate/n-heptane=1:1).

Workup

  1. customplaced on an ice-bath
  2. stirringthe mixture was stirred at room temperature for 30 minutes
  3. customThe solvent was evaporated in vacuo
  4. dissolutionThe oily residue was dissolved in acetone (25 ml)
  5. stirringThe mixture was stirred at room temperature for 120 h
  6. filtrationThe mixture was filtered
  7. customthe solvent was evaporated in vacuo
  8. additiona mixture of ethyl acetate and n-heptane (2:3) as eluent
  9. customCollecting the proper fractions

Sources & evidence

ORD record
ord-b3a7936eeb82434b8a772a230bd5d284
Source dataset
uspto-grants-1994_09
Patent number
US05348965

Reaction notes

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