Hydrochloric Acid → 1-(3-Cyclohexylidene-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)-4-(4-methoxyphenyl)piperazine hydrochloride

HRID 1272294Notes

Reaction equation

HRID 1272294 reaction equation
[ClH:1].[CH:2]1([C:8]2(O)[C:12]3[C:13]([CH3:33])=[C:14]([N:19]4[CH2:24][CH2:23][N:22]([C:25]5[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=5)[CH2:21][CH2:20]4)[C:15]([CH3:18])=[C:16]([CH3:17])[C:11]=3[O:10][C:9]2([CH3:35])[CH3:34])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1>C1COCC1.CO>[ClH:1].[C:2]1(=[C:8]2[C:12]3[C:13]([CH3:33])=[C:14]([N:19]4[CH2:20][CH2:21][N:22]([C:25]5[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=5)[CH2:23][CH2:24]4)[C:15]([CH3:18])=[C:16]([CH3:17])[C:11]=3[O:10][C:9]2([CH3:35])[CH3:34])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 101627441-(3-Cyclohexyl-3-hydroxy-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)-4-(4-methoxyphenyl)piperazine

Product 1

HCID 229355891-(3-Cyclohexylidene-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)-4-(4-methoxyphenyl)piperazine hydrochlorideYield 75%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Concentrated hydrochloric acid (0.5 mL) was added to a solution of 1-(3-cyclohexyl-3-hydroxy-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)-4-(4-methoxyphenyl)piperazine (670 mg, 1.4 mmol) obtained in Example 43 in THF (5 ml) and methanol (5 ml) and the mixture was stirred at room temperature for 12 hours. The reaction mixture was concentrated under reduced pressure and the residue was made to basic with 10% aqueous potassium carbonate. The mixture was extracted with ethyl acetate. The organic extract was washed with water and saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was treated with 4N hydrochloric acid in ethyl acetate solution and the title compound was crystallized from ethanol-diisopropyl ether to obtain 520 mg (yield 75%). mp. 220–222° C.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. extractionThe mixture was extracted with ethyl acetate
  3. extractionThe organic extract
  4. washwas washed with water and saturated aqueous sodium chloride
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. additionThe crude product was treated with 4N hydrochloric acid in ethyl acetate solution
  8. customthe title compound was crystallized from ethanol-diisopropyl ether
  9. customto obtain 520 mg (yield 75%)

Sources & evidence

ORD record
ord-9c996228c8c64792b4854a06ded4b19e
Source dataset
uspto-grants-2007_04
Patent number
US07208495B2

Reaction notes

Loading…