Hydrochloric Acid → HCID 18456069, compound

HRID 1272336Notes

Reaction equation

HRID 1272336 reaction equation
[BH4-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][N:13]([C:16]3[C:17]([CH3:30])=[C:18]([CH3:29])[C:19]4[O:23][C:22]([CH3:25])([CH3:24])[C:21](=O)[C:20]=4[C:27]=3[CH3:28])[CH2:12][CH2:11]2)=[CH:6][CH:5]=1.Cl.[CH2:32]([N:34](CC)[CH2:35][CH3:36])[CH3:33].CS([Cl:43])(=O)=O.N1CCCC1>C1COCC1.ClCCl.C(=O)(O)[O-].[Na+].CO>[ClH:43].[F:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][N:13]([C:16]3[C:17]([CH3:30])=[C:18]([CH3:29])[C:19]4[O:23][C:22]([CH3:24])([CH3:25])[CH:21]([N:34]5[CH2:35][CH2:36][CH2:33][CH2:32]5)[C:20]=4[C:27]=3[CH3:28])[CH2:12][CH2:11]2)=[CH:6][CH:5]=1

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 31268PyrrolidineHCID 31297Methanesulfonyl chlorideHCID 4311764Sodium borohydrideHCID 22935607HCID 22935607, compound

Product 1

HCID 18456069HCID 18456069, compoundYield 19%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Sodium borohydride (106 mg, 2.8 mmol) was added to a solution of 5-(4-(4-fluorophenyl)piperazin-1-yl)-2,2,4,6,7-pentamethyl-1-benzofuran-3(2H)-one (268 mg, 0.7 mmol) obtained in Reference Example 45 in THF (1.5 mL) and methanol (4.5 mL) at room temperature and stirred for 16 hours. The resulting mixture was cooled with ice, made to acidic by 1N hydrochloric acid, and extracted with ethyl acetate. The organic extract was washed with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified with silica gel column chromatography (hexane/ethyl acetate=4/1). The obtained crystals and triethylamine (0.084 mL, 0.6 mmol) were dissolved in dichloromethane (1 ml), and then methane sulfonyl chloride (0.023 mL, 0.3 mmol) was added under ice cooling. The reaction mixture was stirred for 30 minutes with ice cooling. To the mixture was added pyrrolidine (0.125 mL, 1.5 mmol). After stirring for 1 hour under ice cooling, the resulting mixture was diluted with saturated aqueous sodium bicarbonate and 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 residue was purified with silica gel column chromatography (hexane/ethyl acetate=1/1) and it was treated with a solution of hydrogenchloride in ethyl acetate to obtain 27 mg (yield 8%) of the title compound.

Workup

  1. temperatureThe resulting mixture was cooled with ice
  2. extractionextracted with ethyl acetate
  3. extractionThe organic extract
  4. washwas washed with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified with silica gel column chromatography (hexane/ethyl acetate=4/1)
  8. stirringAfter stirring for 1 hour under ice cooling
  9. extractionextracted with ethyl acetate
  10. extractionThe organic extract
  11. washwas washed with water and saturated aqueous sodium chloride
  12. dry with materialdried over anhydrous sodium sulfate
  13. concentrationconcentrated under reduced pressure
  14. customThe residue was purified with silica gel column chromatography (hexane/ethyl acetate=1/1) and it
  15. additionwas treated with a solution of hydrogenchloride in ethyl acetate

Sources & evidence

ORD record
ord-d349afa77d71452ab7a161f16abd8abb
Source dataset
uspto-grants-2007_04
Patent number
US07208495B2

Reaction notes

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