Sulfuric Acid → 6,6-Dimethyl-1,2,6,7-tetrahydrodicyclopenta[b,d]thiophen-3(5H)-one

HRID 592541Notes

Reaction equation

HRID 592541 reaction equation
Cl[CH2:2][CH2:3][C:4]([C:6]1[S:10][C:9]2[CH2:11][C:12]([CH3:15])([CH3:14])[CH2:13][C:8]=2[CH:7]=1)=[O:5].S(=O)(=O)(O)O.P([O-])([O-])(O)=O.[K+].[K+].C(OCC)(=O)C>O>[CH3:14][C:12]1([CH3:15])[CH2:13][C:8]2[C:7]3[CH2:2][CH2:3][C:4](=[O:5])[C:6]=3[S:10][C:9]=2[CH2:11]1

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 8857Ethyl AcetateHCID 24450Potassium Phosphate, DibasicHCID 580442953-Chloro-1-(5,5-dimethyl-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl)propan-1-one

Product 1

HCID 580436356,6-Dimethyl-1,2,6,7-tetrahydrodicyclopenta[b,d]thiophen-3(5H)-oneYield 37%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer was charged with crude 106e (2.86 g, 10.0 mmol presuming quantitative yield) and 98% sulfuric acid. The reaction mixture was heated in a 90° C. oil bath overnight. The reaction mixture was placed into an ice/acetone bath, and a cold (5° C.) solution of dipotassium hydrogen phosphate (105 g, 0.603 mol) in water (300 mL) was added in one portion. The resulting mixture was shaken with ethyl acetate (300 mL) and filtered. The filter cake was washed with ethyl acetate (100 mL). The ethyl acetate layer of the filtrate was separated, dried over sodium sulfate and evaporated under reduced pressure on a rotary evaporator. the resulting residue was purified by flash column chromatography (silica, 80:20 hexanes/ethyl acetate) to afford 106f in 37% yield over two steps (683 mg) as an amorphous brown solid: mp 60-62° C.; 1H NMR (500 MHz, CDCl3) δ 2.92-2.87 (m, 4H), 2.79 (s, 2H), 2.53 (s, 2H), 1.26 (s, 6H); LCMS (ESI+) m/z 207.0 (M+H)

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. customThe reaction mixture was placed into an ice/acetone bath
  3. filtrationfiltered
  4. washThe filter cake was washed with ethyl acetate (100 mL)
  5. customThe ethyl acetate layer of the filtrate was separated
  6. dry with materialdried over sodium sulfate
  7. customevaporated under reduced pressure on a rotary evaporator
  8. customthe resulting residue was purified by flash column chromatography (silica, 80:20 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-21176e4898804a61bd8c4a596878be96
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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