Hydrochloric Acid → (2S)-7-hydroxy-2-methyl-2-(trifluoromethyl)-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one

HRID 633710Notes

Reaction equation

HRID 633710 reaction equation
Br.[CH3:2][C@@:3]1([C:9]([F:12])([F:11])[F:10])[CH2:7][NH:6][C:5]([NH2:8])=[N:4]1.C[O-].[Na+].[C:16](OCC)(=[O:23])[CH2:17][C:18](OCC)=[O:19].Cl>CO>[OH:23][C:16]1[N:8]=[C:5]2[NH:4][C@:3]([CH3:2])([C:9]([F:12])([F:10])[F:11])[CH2:7][N:6]2[C:18](=[O:19])[CH:17]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7761Diethyl MalonateHCID 10942334Sodium MethoxideHCID 178419517HCID 178419517, compound

Product 1

HCID 136069601(2S)-7-hydroxy-2-methyl-2-(trifluoromethyl)-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)-oneYield 107.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

36.90 g (148.76 mmol) of (S)-4-methyl-4-trifluoromethyl-4,5-dihydro-1H-imidazol-2-ylamine hydrobromide and 24.10 g (446 mmol) of sodium methoxide are added to a mixture of 29.50 g (216.43 mmol) of diethyl malonate in 200 mL of methanol. The resulting mixture is refluxed for 18 hours. After cooling, the mixture obtained is concentrated to dryness under vacuum. 65 mL of cold water are added to the residue obtained, to obtain a thick suspension, to which is added 25% hydrochloric acid to pH 5. The resulting suspension is stirred in an ice bath for 3 hours and then filtered. The insoluble matter obtained is rinsed with water and then dried to give 37.60 g of (S)-7-hydroxy-2-methyl-2-trifluoromethyl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one in the form of a white solid, the characteristics of which are as follows:

Workup

  1. temperatureThe resulting mixture is refluxed for 18 hours
  2. temperatureAfter cooling
  3. customthe mixture obtained
  4. concentrationis concentrated to dryness under vacuum
  5. addition65 mL of cold water are added to the residue
  6. customobtained
  7. customto obtain a thick suspension
  8. filtrationfiltered
  9. customThe insoluble matter obtained
  10. washis rinsed with water
  11. customdried

Sources & evidence

ORD record
ord-43503273fe1b44dd9d333b8bf87d22e6
Source dataset
uspto-grants-2016_04
Patent number
US09321790B2

Reaction notes

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