4-Toluenesulfonyl chloride → HCID 90023452, compound

HRID 1484504Notes

Reaction equation

HRID 1484504 reaction equation
O[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH2:10][O:11][CH3:12])[C:4]=1[CH:13]([OH:18])[C:14]([CH3:17])([CH3:16])[CH3:15].C([Li])CCC.CCCCCC.CC1C=CC(S(Cl)(=O)=O)=CC=1>C1COCC1>[C:14]([CH:13]1[C:4]2[C:3](=[CH:8][CH:7]=[CH:6][C:5]=2[O:9][CH2:10][O:11][CH3:12])[CH2:2][O:18]1)([CH3:15])([CH3:16])[CH3:17]

Participants

6

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 8058Hexane2×HCID 118021359HCID 118021359, compound2×HCID 178418339Butyllithium2×

Product 1

HCID 90023452HCID 90023452, compoundYield 93.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1-[2-(hydroxymethyl)-6-(methoxymethoxy)phenyl]-2,2-dimethyl-propan-1-ol (Intermediate 3, 300 mg, 1.18 mmol) in dry THF (5 mL) at OC butyllithium 1.6M solution in hexane (0.74 ml, 1.18 mmol) was slowly added and the reaction mixture was stirred for 5 minutes at the same temperature. 4-methylbenzenesulfonyl chloride (224.89 mg, 1.18 mmol) dissolved in THF (1 ml) was slowly added and the reaction mixture was stirred for 5 minutes at the same temperature. Butyllithium 1.6M solution in hexane (0.74 ml, 1.18 mmol) was slowly added and the reaction mixture was stirred for 30 minutes at at 0° C. The reaction was quenched with water (1 ml), diluted with brine (10 ml) and extracted with ethyl acetate (2×15 ml). The organic layer was dried (Na2SO4), filtered and evaporated and The residue was purified by flash chromatography (Biotage system) on silica gel using a SNAP 25 g as column and cyclohexane/ethyl acetate from 100:0 to 70:30 as eluent affording the title compound (260 mg) as colorless oil.

Workup

  1. additionwas slowly added
  2. stirringthe reaction mixture was stirred for 5 minutes at the same temperature
  3. stirringthe reaction mixture was stirred for 30 minutes at at 0° C
  4. customThe reaction was quenched with water (1 ml)
  5. additiondiluted with brine (10 ml)
  6. extractionextracted with ethyl acetate (2×15 ml)
  7. dry with materialThe organic layer was dried (Na2SO4)
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified by flash chromatography (Biotage system) on silica gel using a SNAP 25 g as column and cyclohexane/ethyl acetate from 100:0 to 70:30 as eluent

Sources & evidence

ORD record
ord-7f6e4e8c8e2742c194adcf96398dfbb9
Source dataset
uspto-grants-2016_08
Patent number
US09422252B2

Reaction notes

Loading…