Hydrochloric Acid → (6-Methoxy-2-cyclohexylbenzo[b]thien-3-yl)[4-[3-(1-pyrrolidinylcarbonyl)propyl]phenyl] methanone

HRID 1756600Notes

Reaction equation

HRID 1756600 reaction equation
[Cl-].[Al+3].[Cl-].[Cl-].[C:5](Cl)(=[O:9])[C:6](Cl)=O.[C:11]1([CH2:17][CH2:18][CH2:19][CH2:20][N:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[CH3:26][O:27][C:28]1[CH:29]=[CH:30][C:31]2C=[C:34]([CH:36]3[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]3)[S:33][C:32]=2[CH:42]=1.Cl.C(=O)([O-])[OH:45].[Na+]>ClCCl.CCCCCC.C(Cl)(Cl)Cl.O.C1COCC1>[CH3:26][O:27][C:28]1[CH:29]=[CH:30][C:31]2[C:6]([C:5]([C:14]3[CH:15]=[CH:16][C:11]([CH2:17][CH2:18][CH2:19][C:20]([N:21]4[CH2:25][CH2:24][CH2:23][CH2:22]4)=[O:45])=[CH:12][CH:13]=3)=[O:9])=[C:34]([CH:36]3[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]3)[S:33][C:32]=2[CH:42]=1

Participants

12

Reactant 6

HCID 313Hydrochloric AcidHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 6451240Aluminum(III) Chloride2×HCID 108794206-Methoxy-2-cyclohexylbenzo[b]thiopheneHCID 194242504-Phenylbutylpyrrolidine

Product 1

HCID 15294978(6-Methoxy-2-cyclohexylbenzo[b]thien-3-yl)[4-[3-(1-pyrrolidinylcarbonyl)propyl]phenyl] methanone

Reagents, catalysts & solvents 5

HCID 962WaterSolvent2×HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent4×HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

200 mg of aluminum chloride is added to 20 mL of dichloromethane, and while this mixture is being agitated at 0° C., 10 mL of a dichloromethane solution of 0.3 mL of oxalyl chloride is added dripwise and agitated for ten minutes at 0° C. 2 mL of a dichloromethane solution of 100 mg of 4-phenylbutylpyrrolidine is added dropwise and agitated for 30 minutes at room temperature. Water is added, and the organic layer is extracted with dichloromethane and dried with anhydrous magnesium sulfate, after which it is condensed. The residue is dissolved in 20 mL of dichloromethane, 100 mg of 6-methoxy-2-cyclohexylbenzo[b]thiophene and 200 mg of aluminum chloride are added, and this mixture is agitated for two hours at room temperature. 1 mL of THF, 0.3 mL of 20% hydrochloric acid, and 1 mL of water are added to the reaction mixture at 25° C. or below, after which a saturated aqueous solution of sodium hydrogencarbonate is added to render the solution alkaline, and the organic layer is extracted with dichloromethane and dried with anhydrous magnesium sulfate. The solvent is distilled off, and the crude product thus obtained is refined by TLC (developing solvent was chloroform: n-hexane=1:5), which gives 54 mg of (6-methoxy-2-cyclohexylbenzo[b]thien-3-yl)[4-[3-(1-pyrrolidinylcarbonyl)propyl]phenyl]methanone.

Workup

  1. stirringagitated for ten minutes at 0° C
  2. stirringagitated for 30 minutes at room temperature
  3. extractionthe organic layer is extracted with dichloromethane
  4. dry with materialdried with anhydrous magnesium sulfate
  5. customcondensed
  6. stirringthis mixture is agitated for two hours at room temperature
  7. extractionthe organic layer is extracted with dichloromethane
  8. dry with materialdried with anhydrous magnesium sulfate
  9. distillationThe solvent is distilled off
  10. customthe crude product thus obtained

Sources & evidence

ORD record
ord-66d67dfb15874f61887fe36c2d0fd41d
Source dataset
uspto-grants-1995_08
Patent number
US05441964

Reaction notes

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