Sulfuric Acid → 4-Pyrimidineethanol, α-(2,4-difluorophenyl)-5-fluoro-β-methyl-α-(1H-1,2,4-triazol-1-ylmethyl)-, 4-(dihydrogen phosphate), (αR,βS)-

HRID 1006651Notes

Reaction equation

HRID 1006651 reaction equation
[P:1]([O:23][C@@:24]([C:40]1[CH:45]=[CH:44][C:43]([F:46])=[CH:42][C:41]=1[F:47])([C@H:31]([C:33]1[C:38]([F:39])=[CH:37][N:36]=[CH:35][N:34]=1)[CH3:32])[CH2:25][N:26]1[CH:30]=[N:29][CH:28]=[N:27]1)([O:13]CC1C(F)=CC=CC=1Cl)([O:3]CC1C(F)=CC=CC=1Cl)=[O:2].[OH-].[Na+].S(=O)(=O)(O)O>[Pd].C1(C)C=CC=CC=1.O>[P:1]([OH:13])([OH:3])([O:23][C@@:24]([C:40]1[CH:45]=[CH:44][C:43]([F:46])=[CH:42][C:41]=1[F:47])([C@H:31]([C:33]1[C:38]([F:39])=[CH:37][N:36]=[CH:35][N:34]=1)[CH3:32])[CH2:25][N:26]1[CH:30]=[N:29][CH:28]=[N:27]1)=[O:2]

Participants

7

Reactant 3

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 57266038Bis(2-chloro-6-fluorobenzyl) (2r,3s)-2-(2,4-difluorophenyl)-3-(5-fluoro-4-pyrimidinyl)-1-(1h-1,2,4-triazol-1-yl)-2-butyl phosphate

Product 1

HCID 235198664-Pyrimidineethanol, α-(2,4-difluorophenyl)-5-fluoro-β-methyl-α-(1H-1,2,4-triazol-1-ylmethyl)-, 4-(dihydrogen phosphate), (αR,βS)-Yield 68.2%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture of the compound of step (a) (50 g, 70 mmol), sodium hydroxide (8.40 g, 210 mmol) and 5% palladium on carbon catalyst (10 g) in toluene (450 ml) and water (150 ml) was hydrogenated at room temperature and 414 kPa (60 p.s.i.) for 24 hours. The reaction mixture was filtered through celite (trade mark) and the toluene layer separated and discarded. The aqueous layer was then washed with methylene chloride (2×75 ml) and toluene (2×75 ml) and then cooled to 0° C. whereupon sulphuric acid (10.3 g, 105 mmol) was added. After granulating at 0° C. for 1 hour the product was filtered, washed with water (60 ml) and dried under vacuum at 50° C. for 16 hours to give the title compound (20.5 g, 68%). The proton NMR data was identical to that obtained in Example 3(b).

Workup

  1. customwas hydrogenated at room temperature
  2. filtrationThe reaction mixture was filtered through celite (trade mark)
  3. customthe toluene layer separated
  4. washThe aqueous layer was then washed with methylene chloride (2×75 ml) and toluene (2×75 ml)
  5. additionwas added
  6. waitAfter granulating at 0° C. for 1 hour
  7. filtrationthe product was filtered
  8. washwashed with water (60 ml)
  9. customdried under vacuum at 50° C. for 16 hours

Sources & evidence

ORD record
ord-65b0a4e02a49496aa93266afe25b4b6c
Source dataset
uspto-grants-2004_09
Patent number
US06790957B2

Reaction notes

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