4-Toluenesulfonyl chloride → HCID 10598185, compound

HRID 1460657Notes

Reaction equation

HRID 1460657 reaction equation
O[CH2:2][CH2:3][O:4][CH:5]=[C:6]([C:13]1[S:14][CH:15]=[CH:16][C:17]=1[CH3:18])[C:7]1[S:8][CH:9]=[CH:10][C:11]=1[CH3:12].C([Li])CCC.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.S(C1C=CC(C)=CC=1)([O-])(=O)=O.[NH:46]1[CH2:56][CH2:55][CH2:54][CH:48]([C:49]([O:51][CH2:52][CH3:53])=[O:50])[CH2:47]1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.O>[CH2:52]([O:51][C:49]([C@@H:48]1[CH2:54][CH2:55][CH2:56][N:46]([CH2:2][CH2:3][O:4][CH:5]=[C:6]([C:7]2[S:8][CH:9]=[CH:10][C:11]=2[CH3:12])[C:13]2[S:14][CH:15]=[CH:16][C:17]=2[CH3:18])[CH2:47]1)=[O:50])[CH3:53]

Participants

9

Reactant 6

HCID 73974-Toluenesulfonyl chlorideHCID 11430Potassium CarbonateHCID 85570p-ToluenesulfonateHCID 98969Ethyl nipecotateHCID 10802731HCID 10802731, compoundHCID 178418339Butyllithium

Product 1

HCID 10598185HCID 10598185, compoundYield 31.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent2×

Conditions

Temperature
0 °C

Procedure

The above alcohol (0.53 g, 0.0019 mol) was dissolved in dry toluene (20 ml) and the solution was cooled to 0° C. A solution of n-butyllithium (2.5M in hexane) (0.9 ml, 0.0023 mol) was introduced, and the reaction mixture was allowed to stand at 0° C. for 1 h after which time a solution of p-toluenesulphonyl chloride (0.47 g, 0.0025 mol) in toluene (10 ml) was added. The mixture was left at room temperature for 20 h and to the resulting tosylate solution was added the (R)-enantiomer of ethyl nipecotate (0.59 g, 0.0038 mol) and powdered, dried potassium carbonate (1.04 g, 0.0075 mol). The temperature was increased to 80° C. and maintained for 50 h. The reaction mixture was cooled and water (50 ml) was added. The toluene phase was separated and the water phase was extracted with ethyl acetate (50 ml). The combined organic extracts were dried (MgSO4) and evaporated to give an oil, which was purified by flash chromatography on silica gel. Elution with cyclohexane/ethyl acetate (19/1 - 5/1) provided the title compound (0.25 g, 31%) as a gum. TLC: rf 0.26 (SiO2 ; heptane/THF 7/3).

Workup

  1. temperatureThe temperature was increased to 80° C.
  2. temperaturemaintained for 50 h
  3. temperatureThe reaction mixture was cooled
  4. customThe toluene phase was separated
  5. extractionthe water phase was extracted with ethyl acetate (50 ml)
  6. dry with materialThe combined organic extracts were dried (MgSO4)
  7. customevaporated
  8. customto give an oil, which
  9. customwas purified by flash chromatography on silica gel
  10. washElution with cyclohexane/ethyl acetate (19/1 - 5/1)

Sources & evidence

ORD record
ord-49cd889a0c704a4e853aef9816241546
Source dataset
uspto-grants-1991_12
Patent number
US05071859

Reaction notes

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