Dimethylamine → N,N-dimethylpiperidine-3-carboxamide

HRID 2234658Notes

Reaction equation

HRID 2234658 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([C:14]([OH:16])=O)[CH2:9]1)=O)(C)(C)C.Cl[C:18]1N=C(Cl)N=[C:20](OC)[N:19]=1.CN1CCOCC1.CNC.FC(F)(F)C(O)=O>C1COCC1.ClCCl.O>[CH3:18][N:19]([CH3:20])[C:14]([CH:10]1[CH2:11][CH2:12][CH2:13][NH:8][CH2:9]1)=[O:16]

Participants

9

Reactant 5

HCID 674DimethylamineHCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 192672,4-Dichloro-6-methoxy-3,5-triazineHCID 27356471-((Tert-butoxy)carbonyl)piperidine-3-carboxylic acid

Product 1

HCID 18760276N,N-dimethylpiperidine-3-carboxamideYield 74.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of piperidine-1,3-dicarboxylic acid 1-tert-butyl ester (1.0 g, 4.36 mmol) in THF (20 mL) was added 2,4-Dichloro-6-methoxy-[1,3,5]triazine (765 mg, 4.36 mmol) and N-methyl morpholine (1.44 mL, 13 mmol). The mixture was stirred at room temperature for 1 h. A dimethylamine solution in THF (10 mL, 2.0 M, 21.3 mmol) was added in one portion. The mixture was stirred at room temperature for 15 h. Water (2.0 mL) was added and the mixture was concentrated in vacuo. The residue was partitioned between ethyl acetate (20 mL) and hydrochloric acid (aqueous 1 N, 15 mL). The organic layer was washed with sodium bicarbonate (sat. 10 mL) and brine (10 mL). It was then dried over sodium sulfate, filtered and concentrated in vacuo to give the crude product (890 mg, 79%). The crude material was dissolved in dichloromethane (3.0 mL) and trifluoroacetic acid (3.0 mL) was added. The mixture was stirred at room temperature for 90 min. It was then concentrated in vacuo. The residue was taken into saturated aqueous sodium bicarbonate (10 mL) and extracted three times with chloroform (15 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo to give 510 mg (74% over 2 steps) piperidine-3-carboxylic acid dimethylamide, which was used directly in the next step.

Workup

  1. stirringThe mixture was stirred at room temperature for 15 h
  2. concentrationthe mixture was concentrated in vacuo
  3. customThe residue was partitioned between ethyl acetate (20 mL) and hydrochloric acid (aqueous 1 N, 15 mL)
  4. washThe organic layer was washed with sodium bicarbonate (sat. 10 mL) and brine (10 mL)
  5. dry with materialIt was then dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give the crude product (890 mg, 79%)
  9. stirringThe mixture was stirred at room temperature for 90 min
  10. concentrationIt was then concentrated in vacuo
  11. extractionextracted three times with chloroform (15 mL)
  12. dry with materialThe combined organic phases were dried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a0367d397e5b4ef0b53f1c43b7e15377
Source dataset
uspto-grants-2010_05
Patent number
US07709645B2

Reaction notes

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