Hydrochloric Acid → 4-(2-{4-[2-Hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]piperazin-1-yl}-1-methylethyl)-2-(methyloxy)benzonitrile

HRID 1187126Notes

Reaction equation

HRID 1187126 reaction equation
[CH3:1][O:2][C:3]1[CH:10]=[C:9]([CH:11]([CH3:14])[CH:12]=O)[CH:8]=[CH:7][C:4]=1[C:5]#[N:6].Cl.[OH:16][CH:17]([C:25]1[CH:34]=[CH:33][C:28]2[C:29](=[O:32])[O:30][CH2:31][C:27]=2[C:26]=1[CH3:35])[CH2:18][N:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl>ClCCl>[OH:16][CH:17]([C:25]1[CH:34]=[CH:33][C:28]2[C:29](=[O:32])[O:30][CH2:31][C:27]=2[C:26]=1[CH3:35])[CH2:18][N:19]1[CH2:24][CH2:23][N:22]([CH2:12][CH:11]([C:9]2[CH:8]=[CH:7][C:4]([C:5]#[N:6])=[C:3]([O:2][CH3:1])[CH:10]=2)[CH3:14])[CH2:21][CH2:20]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 5049666Sodium triacetoxyborohydrideHCID 666465015-(1-hydroxy-2-piperazin-1-ylethyl)-4-methyl-3H-2-benzofuran-1-one;hydrochlorideHCID 772312582-Methoxy-4-(1-oxopropan-2-yl)benzonitrile

Product 1

HCID 498010454-(2-{4-[2-Hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]piperazin-1-yl}-1-methylethyl)-2-(methyloxy)benzonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 2-methoxy-4-(1-oxopropan-2-yl)benzonitrile (0.020 g, 0.106 mmol) were added dichloromethane (15 mL) and 5-[1-hydroxy-2-(piperazin-1-yl)ethyl]-4-methyl-2-benzofuran-1(3H)-one hydrochloride [(0.037 g, 0.116 mmol), in dichloromethane (2 mL), and triethylamine (0.029 mL, 0.211 mmol)], and the mixture was stirred at room temperature for 0.5 h. Sodium triacetoxyborohydride (0.112 g, 0.529 mmol) was added, and the reaction mixture was stirred at room temperature for 24 h. The reaction was quenched with water (5 mL), and the organics were extracted with EtOAc (2×40 mL). The combined organic layers were washed with water (20 mL) and brine (20 mL) and dried (MgSO4). Filtration followed by concentration afforded an oily residue, which was purified via mass-directed reverse-phase HPLC followed by evaporation and drying of the pure fraction obtained which then converted to HCl salt by triturating in 1M HCl in diethyl ether (0.50 mL, 2 h). Evaporation and dried under vacuum provided 4-(2-{4-[2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]piperazin-1-yl}-1-methylethyl)-2-(methyloxy)benzonitrile.

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 24 h
  2. customThe reaction was quenched with water (5 mL)
  3. extractionthe organics were extracted with EtOAc (2×40 mL)
  4. washThe combined organic layers were washed with water (20 mL) and brine (20 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationFiltration
  7. concentrationfollowed by concentration
  8. customafforded an oily residue, which
  9. customwas purified via mass-directed reverse-phase HPLC
  10. customfollowed by evaporation
  11. customdrying of the pure fraction
  12. customobtained which
  13. customby triturating in 1M HCl in diethyl ether (0.50 mL, 2 h)
  14. customEvaporation
  15. customdried under vacuum

Sources & evidence

ORD record
ord-f8fca455bc644438ad50bbca0759a728
Source dataset
uspto-grants-2014_03
Patent number
US08673920B2

Reaction notes

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