4-Toluenesulfonyl chloride → HCID 15254221, compound

HRID 1190981Notes

Reaction equation

HRID 1190981 reaction equation
[CH3:1][C:2]1([CH3:9])[CH2:7][CH2:6][CH2:5][CH:4]([OH:8])[CH2:3]1.C(N(CC)CC)C.[C:17]1([CH3:27])[CH:22]=[CH:21][C:20]([S:23](Cl)(=[O:25])=[O:24])=[CH:19][CH:18]=1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:27][C:17]1[CH:22]=[CH:21][C:20]([S:23]([O:8][CH:4]2[CH2:5][CH2:6][CH2:7][C:2]([CH3:9])([CH3:1])[CH2:3]2)(=[O:25])=[O:24])=[CH:19][CH:18]=1

Participants

6

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 79105Cyclohexanol, 3,3-dimethyl-

Product 1

HCID 15254221HCID 15254221, compoundYield 70.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Under a nitrogen atmosphere, add 3,3-dimethylcyclohexanol (1 g, 9.75 mmol), DMAP (238 mg, 1.95 mmol), triethylamine (2.70 mL, 19.5 mmol), and p-toluenesulfonyl chloride (2.045 g, 10.72 mmol) to DCM (25 mL) at 0° C. Stir the mixture for 1 h at 0° C. and warm to room temperature overnight. Add saturated aqueous NaHCO3 (20 mL) and separate the layers. Extract the aqueous layer with DCM (3×20 mL). Wash the combined organic extracts with water and brine. Dry the organic phase over Na2SO4, filter, and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel (45 g, pre-packed cartridge) eluting with hexane/EtOAc (1:0 to 1:1 gradient over 60 min, 80 mL/min) to obtain the desired intermediate as a clear oil (1.93 g, 70%). MS (APCI+) m/z: 283 (M+H)+.

Workup

  1. temperaturewarm to room temperature overnight
  2. customAdd saturated aqueous NaHCO3 (20 mL) and separate the layers
  3. extractionExtract the aqueous layer with DCM (3×20 mL)
  4. washWash the combined organic extracts with water and brine
  5. dry with materialDry the organic phase over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. customPurify the crude mixture by chromatography on silica gel (45 g, pre-packed cartridge)
  9. washeluting with hexane/EtOAc (1:0 to 1:1 gradient over 60 min, 80 mL/min)

Sources & evidence

ORD record
ord-f770836b010049e4b52bb4764ad57303
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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