4-Toluenesulfonyl chloride → HCID 67960190, compound

HRID 527603Notes

Reaction equation

HRID 527603 reaction equation
O[CH2:2][C:3]1([C:6]2[C:11]([O:12][CH2:13][O:14][CH3:15])=[CH:10][CH:9]=[CH:8][C:7]=2[CH2:16][OH:17])[CH2:5][CH2:4]1.[Li]CCCC.CCCCCC.S(Cl)(C1C=CC(C)=CC=1)(=O)=O>O1CCCC1>[CH3:15][O:14][CH2:13][O:12][C:11]1[C:6]2[C:3]3([CH2:2][O:17][CH2:16][C:7]=2[CH:8]=[CH:9][CH:10]=1)[CH2:4][CH2:5]3

Participants

6

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 8058Hexane2×HCID 67958489HCID 67958489, compound2×HCID 178418339Butyllithium2×

Product 1

HCID 67960190HCID 67960190, compoundYield 92.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (2-[1-(hydroxymethyl)cyclopropyl]-3-{[(methyloxy)methyl]oxy}phenyl)methanol (Intermediate 134, 450 mg) in dry tetrahydrofuran (10 ml) at 0° C., a solution of BuLi in hexane (1.6M, 1.180 mL, 1.889 mmol) was slowly added and the reaction mixture was stirred for 15 minutes at the same temperature. A solution of tosyl chloride (360 mg, 1.889 mmol) in dry tetrahydrofuran (5 ml) was slowly added and the reaction mixture was stirred for 15 minutes at 0° C. A second equivalent of a solution of BuLi in hexane (1.6M, 1.180 mL, 1.889 mmol) was added and the reaction mixture was stirred for 30 minutes at the same temperature. The reaction was quenched with an aqueous saturated solution of NaHCO3 (10 ml) diluted with water (10 ml) and extracted with ethyl acetate (2×30 ml). The organic layer was dried over sodium sulphate, filtered and evaporated and the residue was purified by flash chromatography (Biotage system) on silica gel using a 25 g SNAP column and cyclohexane/ethyl acetate as eluents from 100:0 to 8:2. This afforded the title compound 5-{[(methyloxy)methyl]oxy}-1H-spiro[2-benzopyran-4,1′-cyclopropane] as a colourless oil (385 mg).

Workup

  1. stirringthe reaction mixture was stirred for 15 minutes at 0° C
  2. stirringthe reaction mixture was stirred for 30 minutes at the same temperature
  3. customThe reaction was quenched with an aqueous saturated solution of NaHCO3 (10 ml)
  4. additiondiluted with water (10 ml)
  5. extractionextracted with ethyl acetate (2×30 ml)
  6. dry with materialThe organic layer was dried over sodium sulphate
  7. filtrationfiltered
  8. customevaporated
  9. customthe residue was purified by flash chromatography (Biotage system) on silica gel using a 25 g SNAP column and cyclohexane/ethyl acetate as eluents from 100:0 to 8:2

Sources & evidence

ORD record
ord-4eb3ad69b170428bb3de1a17997af70a
Source dataset
uspto-grants-2016_05
Patent number
US09346790B2

Reaction notes

Loading…