Diethyl Pyrocarbonate → 4-bromo-N-[(3R,4R)-3-(3,4-dichlorophenyl)-1-{[1-(hydroxyacetyl)piperidin-4-yl]carbonyl}piperidin-4-yl]-N-methylbenzamide monohydrate

HRID 1260987Notes

Reaction equation

HRID 1260987 reaction equation
[Br:1][C:2]1[CH:25]=[CH:24][C:5]([C:6]([N:8]([C@@H:10]2[CH2:15][CH2:14][NH:13][CH2:12][C@H:11]2[C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([Cl:23])[CH:17]=2)[CH3:9])=[O:7])=[CH:4][CH:3]=1.C(N(CC)CC)C.[OH:33][CH2:34][C:35]([N:37]1[CH2:42][CH2:41][CH:40]([C:43](O)=[O:44])[CH2:39][CH2:38]1)=[O:36].CCOC(OC(OCC)=O)=O>CN(C=O)C.O>[OH2:7].[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]([C@@H:10]2[CH2:15][CH2:14][N:13]([C:43]([CH:40]3[CH2:41][CH2:42][N:37]([C:35](=[O:36])[CH2:34][OH:33])[CH2:38][CH2:39]3)=[O:44])[CH2:12][C@H:11]2[C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([Cl:23])[CH:17]=2)[CH3:9])=[O:7])=[CH:24][CH:25]=1

Participants

7

Reactant 4

HCID 3051Diethyl PyrocarbonateHCID 8471TriethylamineHCID 242848391-Glycoloylpiperidine-4-carboxylic acidHCID 689301054-bromo-N-[(3R,4R)-3-(3,4-dichlorophenyl)piperidin-4-yl]-N-methylbenzamide

Product 1

HCID 689287194-bromo-N-[(3R,4R)-3-(3,4-dichlorophenyl)-1-{[1-(hydroxyacetyl)piperidin-4-yl]carbonyl}piperidin-4-yl]-N-methylbenzamide monohydrateYield 94.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of the compound obtained in step 3 (200 mg), triethylamine (313 μL) and 1-(hydroxyacetyl)piperidine-4-carboxylic acid (101 mg) in DMF (4.5 mL) was added DEPC (87 mg), and the mixture was stirred overnight at room temperature. To the reaction mixture was added water, and the resultant product was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution, 1N hydrochloric acid and brine and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (NH Chromatorex) (solvent gradient; 40→95% ethyl acetate/hexane) to give the title compound (135 mg, 49%) as a white crystal powder.

Workup

  1. extractionthe resultant product was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated aqueous sodium hydrogen carbonate solution, 1N hydrochloric acid and brine
  3. customdried
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (NH Chromatorex) (solvent gradient; 40→95% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-be47747f3774474bb650f508e8ee7043
Source dataset
uspto-grants-2013_06
Patent number
US08470816B2

Reaction notes

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