Triethylamine → 1-propyl-5-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazole-3-carbonitrile

HRID 549239Notes

Reaction equation

HRID 549239 reaction equation
FC(F)(F)C(OC(=O)C(F)(F)F)=O.[CH2:14]([N:17]1[C:21]([CH2:22][CH:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)=[CH:20][C:19]([C:29]([NH2:31])=O)=[N:18]1)[CH2:15][CH3:16].C(N(CC)CC)C>ClCCl>[CH2:14]([N:17]1[C:21]([CH2:22][CH:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)=[CH:20][C:19]([C:29]#[N:31])=[N:18]1)[CH2:15][CH3:16]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 9845Trifluoroacetic anhydrideHCID 671577891-propyl-5-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazole-3-carboxamide

Product 1

HCID 671577501-propyl-5-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazole-3-carbonitrileYield 106%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of trifluoroacetic anhydride (2.50 mL, 17.7 mmol) in dichloromethane (32 mL) was added over a period of ten minutes to a 0° C. solution of 1-propyl-5-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazole-3-carboxamide (4.05 g, 16.1 mmol) and triethylamine (4.89 g, 48.3 mmol) in dichloromethane (32 mL). After the addition was complete, the cooling bath was removed and the solution was stirred for three hours. The solution was washed with 2 M aqueous sodium carbonate. The aqueous layer was extracted three times with tert-butyl methyl ether. The organic layers were combined, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by automated flash chromatography (eluting with 40% to 70% ethyl acetate in hexane) to provide 3.98 g of 1-propyl-5-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazole-3-carbonitrile as a pale yellow oil.

Workup

  1. additionAfter the addition
  2. customthe cooling bath was removed
  3. washThe solution was washed with 2 M aqueous sodium carbonate
  4. extractionThe aqueous layer was extracted three times with tert-butyl methyl ether
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by automated flash chromatography (eluting with 40% to 70% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-06267feec9794738995cf08950a373d3
Source dataset
uspto-grants-2011_05
Patent number
US07943636B2

Reaction notes

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