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

HRID 2064220Notes

Reaction equation

HRID 2064220 reaction equation
[Cl:1][C:2]1[C:17]([O:18][CH:19]([CH3:21])[CH3:20])=[CH:16][C:5]2[N:6]([CH:10]3[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]3)[C:7](=[O:9])[NH:8][C:4]=2[CH:3]=1.[O:22]1[CH2:27][CH2:26][C:25](=O)[CH2:24][CH2:23]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(N(CC)CC)C>ClCCl>[ClH:1].[Cl:1][C:2]1[C:17]([O:18][CH:19]([CH3:21])[CH3:20])=[CH:16][C:5]2[N:6]([CH:10]3[CH2:11][CH2:12][N:13]([CH:25]4[CH2:26][CH2:27][O:22][CH2:23][CH2:24]4)[CH2:14][CH2:15]3)[C:7](=[O:9])[NH:8][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 121599Tetrahydro-4H-pyran-4-oneHCID 5049666Sodium triacetoxyborohydrideHCID 598501865-Chloro-6-[(1-methylethyl)oxy]-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one

Product 1

HCID 691285705-Chloro-6-[(1-methylethyl)oxy]-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one hydrochlorideYield 26,666.699%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 5-chloro-6-[(1-methylethyl)oxy]-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one (D87, 94 mg, 0.30 mmol) in dichloromethane (3 ml) was treated with tetrahydro-4H-pyran-4-one (0.213 g, 0.21 mmol, 7 eq), sodium triacetoxyborohydride (0.445 g, 0.21 mmol, 7 eq) and triethylamine (0.101 g, 1 mmol, 3 eq) and stirred at room temperature under argon overnight. The mixture was diluted with dichloromethane and washed with aqueous NaOH solution (pH12). The NaOH wash was extracted with dichloromethane (×2) and the combined extracts was washed with aqu, NaOH solution, dried (MgSO4) and concentrated under vacuum. The residue was purified by MDAP to afford the title compound as a white solid (14 mg, 0.04 mol, 13%). M++H=394.2.

Workup

  1. washwashed with aqueous NaOH solution (pH12)
  2. washThe NaOH wash
  3. extractionwas extracted with dichloromethane (×2)
  4. washthe combined extracts was washed with aqu, NaOH solution
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by MDAP

Sources & evidence

ORD record
ord-74987ea991984770bbc8fb6155510f01
Source dataset
uspto-grants-2012_10
Patent number
US08288412B2

Reaction notes

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