Hydrochloric Acid → 6-Methyl-5-[(1-methylethyl)oxy]-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

HRID 2064219Notes

Reaction equation

HRID 2064219 reaction equation
[CH3:1][C:2]1[C:3]([O:18][CH:19]([CH3:21])[CH3:20])=[CH:4][C:5]2[NH:9][C:8](=[O:10])[N:7]([CH:11]3[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]3)[C:6]=2[CH:17]=1.[O:22]1[CH2:27][CH2:26][C:25](=O)[CH2:24][CH2:23]1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+].[ClH:52]>ClCCl.CO>[ClH:52].[CH3:1][C:2]1[C:3]([O:18][CH:19]([CH3:21])[CH3:20])=[CH:4][C:5]2[NH:9][C:8](=[O:10])[N:7]([CH:11]3[CH2:12][CH2:13][N:14]([CH:25]4[CH2:26][CH2:27][O:22][CH2:23][CH2:24]4)[CH2:15][CH2:16]3)[C:6]=2[CH:17]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 121599Tetrahydro-4H-pyran-4-oneHCID 5049666Sodium triacetoxyborohydrideHCID 598501546-Methyl-5-[(1-methylethyl)oxy]-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one

Product 1

HCID 691282956-Methyl-5-[(1-methylethyl)oxy]-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent3×

Procedure

A solution of 6-methyl-5-[(1-methylethyl)oxy]-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one (D77) (assumed 0.14 mmol—crude material) in dichloromethane (2 mL) was treated with tetrahydro-4H-pyran-4-one (1.4 mmol, 140 mg, 10 eq) and triethylamine (1.4 mmol, 141.7 mg, 10 eq) at room temperature under argon, then sodium triacetoxyborohydride (1.4 mmol, 296.8 mg, 10 eq) was added and the mixture was allowed to stir for 3 h and to stand overnight. The mixture was diluted with dichloromethane and treated with aqueous sodium hydroxide so that the pH was maintained around 12. The aqueous phase was extracted, the organics were combined, washed with aqueous sodium hydroxide solution (pH˜12), dried and concentrated under reduced pressure. The residue was purified by chromatography (methanol/dichloromethane, 0-10% 5CV) to give a gum, which was dissolved in dichloromethane and methanol, treated with ethereal hydrogen chloride, then concentrated under reduced pressure to give the title compound as its hydrochloride salt-white solid (0.071 mmol, 29 mg, 51% yield). M+H 374.1.

Workup

  1. waitto stand overnight
  2. temperaturewas maintained around 12
  3. extractionThe aqueous phase was extracted
  4. washwashed with aqueous sodium hydroxide solution (pH˜12)
  5. customdried
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by chromatography (methanol/dichloromethane, 0-10% 5CV)
  8. customto give a gum, which
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9e66d5ead34549a3a35c159fcb3edd8d
Source dataset
uspto-grants-2012_10
Patent number
US08288412B2

Reaction notes

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