Sulfuric Acid → Fosfluconazole

HRID 1006648Notes

Reaction equation

HRID 1006648 reaction equation
[P:1]([O:19][C:20]([C:33]1[CH:38]=[CH:37][C:36]([F:39])=[CH:35][C:34]=1[F:40])([CH2:27][N:28]1[CH:32]=[N:31][CH:30]=[N:29]1)[CH2:21][N:22]1[CH:26]=[N:25][CH:24]=[N:23]1)([O:11]CC1C=CC=CC=1)([O:3]CC1C=CC=CC=1)=[O:2].[OH-].[Na+].S(=O)(=O)(O)O>[Pd].O>[P:1]([OH:11])([OH:3])([O:19][C:20]([C:33]1[CH:38]=[CH:37][C:36]([F:39])=[CH:35][C:34]=1[F:40])([CH2:27][N:28]1[CH:32]=[N:31][CH:30]=[N:29]1)[CH2:21][N:22]1[CH:26]=[N:25][CH:24]=[N:23]1)=[O:2]

Participants

6

Reactant 3

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 155094011-(2,4-Difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)-1-(1H-1,2,4-triazol-1-ylmethyl)ethyl bis(phenylmethyl) phosphate

Product 1

HCID 214356FosfluconazoleYield 87%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 962WaterSolvent

Procedure

A slurry of the compound of step (a) (9.80 g, 17.3 mmol), 5% palladium on carbon catalyst (50% wet, 1.0 g) and sodium hydroxide (1.38 g, 34.6 mmol) in water (26 ml) was hydrogenated at room temperature and 414 kPa (60 p.s.i.) for 20 hours. The solution was filtered through a pad of celite (trade mark) and washed with water (5 ml). The toluene was separated and the aqueous phase cooled to 0° C. whereupon sulphuric acid (1.70 g, 17.3 mmol) was added. The resulting slurry was granulated at 0° C. for 1 hour and then filtered, washed with water (2×5 ml) and dried under vacuum at 50° C. to give the title compound (5.80 g, 87%). m.p. 223-224° C.

Workup

  1. customwas hydrogenated at room temperature
  2. filtrationThe solution was filtered through a pad of celite (trade mark)
  3. washwashed with water (5 ml)
  4. customThe toluene was separated
  5. additionwas added
  6. waitThe resulting slurry was granulated at 0° C. for 1 hour
  7. filtrationfiltered
  8. washwashed with water (2×5 ml)
  9. customdried under vacuum at 50° C.

Sources & evidence

ORD record
ord-d6ac5742d2af4bf5b2c46cc48e50d9cd
Source dataset
uspto-grants-2004_09
Patent number
US06790957B2

Reaction notes

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