Dichloromethane → 6-[(1-Methylethyl)oxy]-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

HRID 2064093Notes

Reaction equation

HRID 2064093 reaction equation
[CH3:1][CH:2]([O:4][C:5]1[CH:6]=[CH:7][C:8]2[NH:12][C:11](=[O:13])[N:10]([CH:14]3[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)[C:9]=2[CH:20]=1)[CH3:3].[O:21]1[CH2:26][CH2:25][C:24](=O)[CH2:23][CH2:22]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(N(CC)CC)C.[OH-].[Na+].[Cl:51]CCl>>[ClH:51].[CH3:3][CH:2]([O:4][C:5]1[CH:6]=[CH:7][C:8]2[NH:12][C:11](=[O:13])[N:10]([CH:14]3[CH2:15][CH2:16][N:17]([CH:24]4[CH2:25][CH2:26][O:21][CH2:22][CH2:23]4)[CH2:18][CH2:19]3)[C:9]=2[CH:20]=1)[CH3:1]

Participants

7

Reactant 6

HCID 6344Dichloromethane2×HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 121599Tetrahydro-4H-pyran-4-oneHCID 5049666Sodium triacetoxyborohydrideHCID 574239196-[(1-Methylethyl)oxy]-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one

Product 1

HCID 691223526-[(1-Methylethyl)oxy]-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one hydrochlorideYield 33%

Procedure

A solution of 6-[(1-methylethyl)oxy]-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one (D50, 229 mg, 0.89 mmol) in dichloromethane (10 ml) was treated with tetrahydro-4H-pyran-4-one (623 mg, 6.23 mmol), sodium triacetoxyborohydride (1.3 g, 6.23 mmol) and triethylamine (270 mg, 3.67 mmol) and stirred at room temperature for 2 hrs. The mixture was diluted with dichloromethane, then aqueous NaOH solution (pH12) was added and the organic layer separated. The NaOH solution was extracted with dichloromethane (×2) and the combined dichloromethane extracts was washed with aqu, NaOH solution, dried (MgSO4) and concentrated under vacuum to leave a pale orange oil, which was purified by chromatography on silica gel eluting with 0-50% of 10% methanol/dichloromethane: dichloromethane to afford the title compound as a pale orange solid (101 mg, 33%). M++H=360.2 which was converted to its HCl salt.

Workup

  1. customthe organic layer separated
  2. extractionThe NaOH solution was extracted with dichloromethane (×2)
  3. washthe combined dichloromethane extracts was washed with aqu, NaOH solution
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated under vacuum
  6. customto leave a pale orange oil, which
  7. customwas purified by chromatography on silica gel eluting with 0-50% of 10% methanol/dichloromethane

Sources & evidence

ORD record
ord-b4f103c1e69840a4a241233f1b784429
Source dataset
uspto-grants-2012_10
Patent number
US08288413B2

Reaction notes

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