Water → tert-Butyl 1-(4-chlorophthalazin-1-yl)piperidin-4-yl(methyl)carbamate

HRID 2389244Notes

Reaction equation

HRID 2389244 reaction equation
C(=O)([O-])[O-].[K+].[K+].Cl[C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([Cl:18])=[N:10][N:9]=1.[C:19]([O:23][C:24](=[O:33])[N:25]([CH3:32])[CH:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)([CH3:22])([CH3:21])[CH3:20].O>CN1CCCC1>[Cl:18][C:11]1[C:12]2[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:8]([N:29]2[CH2:28][CH2:27][CH:26]([N:25]([CH3:32])[C:24](=[O:33])[O:23][C:19]([CH3:20])([CH3:21])[CH3:22])[CH2:31][CH2:30]2)=[N:9][N:10]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 784901,4-DichlorophthalazineHCID 27568064-N-Boc-4-N-Methyl-aminopiperidine

Product 1

HCID 58157124tert-Butyl 1-(4-chlorophthalazin-1-yl)piperidin-4-yl(methyl)carbamateYield 37%

Reagents, catalysts & solvents 1

HCID 84541-MethylpyrrolidineSolvent

Procedure

Heat a mixture of potassium carbonate (21.23 g, 153 6 mmol), 1,4-dichlorophthalazine (26 g, 128 mmol) and methyl-piperidin-4-yl carbamic acid tert-butyl ester (30.01 g, 134.4 mmol) in N-methylpyrrolidine (200 mL) at 80° C. overnight. Pour the reaction mixture into water, extract with dichloromethane, dry over Na2SO4, and concentrate under reduced pressure. Add diethylether and filter off the resulting solid (4-chlorophethalazin-1-ol from starting material impurity). Concentrate the filtrate. Purify the resulting residue by flash silica gel chromatography (hexane:ethyl acetate=2:1) to provide the title compound as a white solid (17.66 g, 37%). ES/MS m/z (37Cl) 377.0 (M+1).

Workup

  1. temperatureHeat
  2. extractionextract with dichloromethane
  3. dry with materialdry over Na2SO4
  4. concentrationconcentrate under reduced pressure
  5. filtrationAdd diethylether and filter off the resulting solid (4-chlorophethalazin-1-ol from starting material impurity)
  6. concentrationConcentrate the filtrate
  7. customPurify the resulting residue by flash silica gel chromatography (hexane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-4bcf84f14c15404eb1c6e624fada284b
Source dataset
uspto-grants-2012_09
Patent number
US08273742B2

Reaction notes

Loading…