4-Piperidinecarboxamide → HCID 22313260, compound

HRID 965814Notes

Reaction equation

HRID 965814 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]([NH2:9])=O)[CH2:3][CH2:2]1.[O:10]1[CH2:15][CH2:14][CH:13]([C:16](O)=O)[CH2:12][CH2:11]1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[H-].[Al+3].[Li+].[H-].[H-].[H-]>CN(C)C=O.O1CCCC1>[O:10]1[CH2:15][CH2:14][CH:13]([CH2:16][N:1]2[CH2:6][CH2:5][CH:4]([CH2:7][NH2:9])[CH2:3][CH2:2]2)[CH2:12][CH2:11]1

Participants

8

Reactant 5

HCID 37724-PiperidinecarboxamideHCID 81531DiisopropylethylamineHCID 219302Oxane-4-carboxylic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 21226445Aluminium lithium hydride

Product 1

HCID 22313260HCID 22313260, compoundYield 103.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred mixture of piperidine-4-carboxamide (1.28 g, 10 mmol), tetrahydro-2H-pyran-4-carboxylic acid (1.43 g, 11 mmol) and diisopropylethylamine (2.09 mL, 11 mmol) in N,N-dimethylformamide was added HBTU (N-[(1H-1,2,3-benzotriazol-1-yloxy)(dimethylamino)methylene]-N-methylmethanaminium hexafluorophosphate, 4.14 g, 11 mmol) at 0° C. After being stirred for 0.5 h at 0° C., the mixture was stirred for 3 h at ambient temperature. Then, the mixture was partitioned between ethyl acetate and water. After extraction with ethyl acetate, the combined organic extract was washed with brine, dried over magnesium sulfate and concentrated. This crude material was dissolved in tetrahydrofuran (50 mL) and added to the mixture of lithium aluminum hydride (1.90 g, 50 mmol) in tetrahydrofuran (50 mL) at 0° C. Then, the mixture was heated at 40° C. and stirred for 5 h. The mixture was cooled to 0° C. and quenched with sodium sulfate decahydrate (3.8 g) and potassium fluoride (9.0 g). After vigorous stirring for 0.5 h, the insoluble materials were filtered off. The filtrate was concentrated to give 2.19 g (99%) of the title compound as a colorless viscous oil.

Workup

  1. stirringthe mixture was stirred for 3 h at ambient temperature
  2. customThen, the mixture was partitioned between ethyl acetate and water
  3. extractionAfter extraction with ethyl acetate
  4. extractionthe combined organic extract
  5. washwas washed with brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. dissolutionThis crude material was dissolved in tetrahydrofuran (50 mL)
  9. temperatureThen, the mixture was heated at 40° C.
  10. stirringstirred for 5 h
  11. temperatureThe mixture was cooled to 0° C.
  12. customquenched with sodium sulfate decahydrate (3.8 g) and potassium fluoride (9.0 g)
  13. stirringAfter vigorous stirring for 0.5 h
  14. filtrationthe insoluble materials were filtered off
  15. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-d6290f324df8424288e326a89d481324
Source dataset
uspto-grants-2005_10
Patent number
US06951867B2

Reaction notes

Loading…