Formaldehyde → HCID 22648751, compound

HRID 393145Notes

Reaction equation

HRID 393145 reaction equation
[F:1][C:2]([F:15])([F:14])[C:3]1[C:8]([CH:9]([NH2:13])[CH:10]([CH3:12])[CH3:11])=[CH:7][N:6]=[CH:5][N:4]=1.[CH2:16]=[O:17].C(N(CC)CC)C.[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32][C:33](Cl)=[O:34])=[CH:28][CH:27]=1.[CH3:36]O>C1(C)C=CC=CC=1.O>[CH3:16][O:17][CH2:36][N:13]([CH:9]([C:8]1[C:3]([C:2]([F:1])([F:14])[F:15])=[N:4][CH:5]=[N:6][CH:7]=1)[CH:10]([CH3:12])[CH3:11])[C:33](=[O:34])[CH2:32][C:29]1[CH:30]=[CH:31][C:26]([Cl:25])=[CH:27][CH:28]=1

Participants

8

Reactant 5

HCID 712FormaldehydeHCID 887MethanolHCID 8471Triethylamine2×HCID 906924-Chlorophenylacetyl chlorideHCID 22648766HCID 22648766, compound

Product 1

HCID 22648751HCID 22648751, compoundYield 26.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent2×

Procedure

1.0 g (4.6 mmol) of 4-trifluoromethyl-5-[1-amino-2-methylpropyl]pyrimidine, 0.23 g (6.9 mmol)of paraformaldehyde and 0.1 g (9.9 mmol) of triethylamine were dissolved in 50 ml of toluene. Heating and refluxing were carried out for 1 hour while removing water from the reaction system by means of Dean's Stark. The reaction solution was returned to room temperature, and 0.86 g (4.6 mmol) of 4-chlorophenylacetylchloride was dropwise added, followed by stirring for further 2 hours. To this solution, 10 ml of a toluene solution containing 0.2 g (6.2 mmol) of methanol and 0.5 g (4.9 mmol) of triethylamine, was dropwise added, followed by stirring at room temperature for 1 hour. To the reaction solution, 100 mg of water was added, followed by extraction with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off under reduced pressure, and the obtained crude product was purified by silica gel column chromatography (developing solvent/n-hexane:ethyl acetate=3:1) to obtain 0.5 g (yield: 26%) of N-methoxymethyl-N-[2-methyl-1-(4-trifluoromethylpyrimidin-5-yl)propyl]-4-chlorophenylacetamide as colorless transparent crystals (melting point: 142-145° C.).

Workup

  1. temperatureHeating
  2. temperaturerefluxing
  3. customwhile removing water from the reaction system by means of Dean's Stark
  4. customwas returned to room temperature
  5. additionwas dropwise added
  6. stirringby stirring at room temperature for 1 hour
  7. extractionfollowed by extraction with ethyl acetate
  8. washThe obtained organic layer was washed with water
  9. dry with materialdried over anhydrous magnesium sulfate
  10. distillationEthyl acetate was distilled off under reduced pressure
  11. customthe obtained crude product
  12. customwas purified by silica gel column chromatography (developing solvent/n-hexane:ethyl acetate=3:1)

Sources & evidence

ORD record
ord-7de165c3f51f4cea894945e7ef12c5f4
Source dataset
uspto-grants-2004_10
Patent number
US06806230B1

Reaction notes

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