Benzo(B)Thiophene → HCID 12973059, compound

HRID 351335Notes

Reaction equation

HRID 351335 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[CH:7][CH:8]=[CH:9][C:2]1=2.C([Li])(C)(C)C.CCCCC.[CH3:20][N:21]([CH3:35])[C:22]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:27][CH2:26][C:25](=[O:28])[CH2:24][CH2:23]1>C1COCC1>[S:1]1[C:5]([C:25]2([OH:28])[CH2:26][CH2:27][C:22]([N:21]([CH3:20])[CH3:35])([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:23][CH2:24]2)=[CH:4][C:3]2[CH:6]=[CH:7][CH:8]=[CH:9][C:2]1=2

Participants

6

Reactant 4

HCID 7221Benzo(B)ThiopheneHCID 8003PentaneHCID 114244924-(Dimethylamino)-4-phenylcyclohexan-1-oneHCID 178418306HCID 178418306, compound

Product 1

HCID 12973059HCID 12973059, compoundYield 32.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of benzo[b]thiophene (400 mg, 2.98 mmol) in dry THF (20 ml) was cooled to −5° C. under a stream of argon. Tert-butyllithium (3.58 mmol, 2.11 ml of a 1.7 molar pentane solution) was carefully added dropwise, to avoid exceeding a reaction temperature of 0° C. Once all the substance had been added, the reaction mixture was stirred for 2 hours at 0° C. A solution of 4-dimethylamino-4-phenylcyclohexanone (648 mg, 2.98 mmol) in dry THF (5 ml) was then added dropwise at 0° C. The mixture was stirred for 15 minutes at 0° C. and then 6 hours at ambient temperature. The reaction mixture was quenched with saturated ammonium chloride solution (20 ml), the organic phase was separated and the aqueous phase extracted four times with dichloromethane (20 ml). The combined organic phases were dried over sodium sulfate, filtered and the solvent was removed under vacuum. Purification was carried out by flash chromatography over silica gel with cyclohexane/ethylacetate (V:V=1:1). 345 mg 1-benzo[b]thiophen-2-yl-4-dimethylamino-4-phenylcyclohexanol with a melting point of 183–185° C. were obtained.

Workup

  1. customa reaction temperature of 0° C
  2. additionOnce all the substance had been added
  3. stirringThe mixture was stirred for 15 minutes at 0° C.
  4. custom6 hours
  5. customat ambient temperature
  6. customThe reaction mixture was quenched with saturated ammonium chloride solution (20 ml)
  7. customthe organic phase was separated
  8. extractionthe aqueous phase extracted four times with dichloromethane (20 ml)
  9. dry with materialThe combined organic phases were dried over sodium sulfate
  10. filtrationfiltered
  11. customthe solvent was removed under vacuum
  12. customPurification

Sources & evidence

ORD record
ord-8af80b1208264fcc86f996ad570ddb71
Source dataset
uspto-grants-2007_02
Patent number
US07183436B2

Reaction notes

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