4-[6-(2-Ethoxy-phenyl)-pyrimidin-4-ylcarbamoyl]-piperidine-1-carboxylic acid tert-butyl ester → Piperidine-4-carboxylic acid [6-(2-ethoxy-phenyl)-pyrimidin-4-yl]-amide

HRID 1020028Notes

Reaction equation

HRID 1020028 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[O:31])[NH:15][C:16]2[CH:21]=[C:20]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[O:28][CH2:29][CH3:30])[N:19]=[CH:18][N:17]=2)[CH2:10][CH2:9]1)=O)(C)(C)C>ClCCl.C(O)(C(F)(F)F)=O>[CH2:29]([O:28][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[C:20]1[N:19]=[CH:18][N:17]=[C:16]([NH:15][C:14]([CH:11]2[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]2)=[O:31])[CH:21]=1)[CH3:30]

Participants

4

Reactant 1

HCID 595089574-[6-(2-Ethoxy-phenyl)-pyrimidin-4-ylcarbamoyl]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 59508999Piperidine-4-carboxylic acid [6-(2-ethoxy-phenyl)-pyrimidin-4-yl]-amideYield 50%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

To a stirred solution of 4-[6-(2-ethoxy-phenyl)-pyrimidin-4-ylcarbamoyl]-piperidine-1-carboxylic acid tert-butyl ester (IV), (0.500 g, 1.17 mmol) in dry dichloromethane (1.5 ml), TFA (1.5 ml) was added at 0° C. and the reaction mixture was stirred for 2-3 hours. After completion of the reaction (monitored by TLC) the solvent mixture was removed under reduced pressure and dichloromethane was added to the residue. Solid sodium carbonate was added and the mixture was stirred for 3-4 hours. Then it was filtered and washed with dichloromethane. The combined filtrate was concentrated under reduced pressure to obtain a solid which was washed with 10% ethyl acetate/hexane to remove nonpolar impurities, giving piperidine-4-carboxylic acid [6-(2-ethoxy-phenyl)-pyrimidin-4-yl]-amide (compound #1A) as pure white solid (0.19 g, 50%).

Workup

  1. customAfter completion of the reaction (monitored by TLC) the solvent mixture
  2. customwas removed under reduced pressure and dichloromethane
  3. additionwas added to the residue
  4. additionSolid sodium carbonate was added
  5. stirringthe mixture was stirred for 3-4 hours
  6. filtrationThen it was filtered
  7. washwashed with dichloromethane
  8. concentrationThe combined filtrate was concentrated under reduced pressure
  9. customto obtain a solid which
  10. washwas washed with 10% ethyl acetate/hexane
  11. customto remove nonpolar impurities

Sources & evidence

ORD record
ord-d8cc3842871b441584b7fbc3777d0115
Source dataset
uspto-grants-2014_05
Patent number
US08716296B2

Reaction notes

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