Toluene → [4-(4-Fluorophenyl)-2-(methylsulfanyl)-6-(propan-2-yl)pyrimidin-5-yl]methanol

HRID 253045Notes

Reaction equation

HRID 253045 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14](OC)=[O:15])=[C:12]([CH:18]([CH3:20])[CH3:19])[N:11]=[C:10]([S:21][CH3:22])[N:9]=2)=[CH:4][CH:3]=1.C1(C)C=CC=CC=1.[H-].C([Al+]CC(C)C)C(C)C>O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([CH2:14][OH:15])=[C:12]([CH:18]([CH3:20])[CH3:19])[N:11]=[C:10]([S:21][CH3:22])[N:9]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 1140TolueneHCID 11652673Methyl 4-(4-Fluorophenyl)-6-isopropyl-2-(methylthio)pyrimidine-5-carboxylate2×HCID 21225700Diisobutylaluminumhydride

Product 1

HCID 29980411[4-(4-Fluorophenyl)-2-(methylsulfanyl)-6-(propan-2-yl)pyrimidin-5-yl]methanolYield 88%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

20 g (62.5 mmol) of methyl 4-(4′-fluorophenyl)-6-isopropyl-2-methylthio-pyrimidin-5-yl-carboxylate (10) and 300 mL of dry anhydrous toluene were loaded in a IL three-neck round bottomed flask, equipped with a mechanical stirrer and an air duct, and stirred under a nitrogen atmosphere. 100 mmol of diisobutyl aluminum hydride (DIBAI-H) was then added in batches into the mixture while cooling in an ice-salt bath. After TLC assay showed that the starting compound (10) was depleted, the reaction mixture was warmed up to room temperature and further reacted for 2-3 hours. 500 mL of water was then added, and the organic layer was collected, washed with water (200 mL×2) and a saturated solution of sodium chloride (200 mL×1), and then dried overnight over anhydrous magnesium sulfate. The mixture was then filtered, evaporated under reduced pressure to remove the solvent, and recrystallized in ethyl acetate, obtaining 16 g of a white crystal, yield 88%.

Workup

  1. customequipped with a mechanical stirrer
  2. temperaturewhile cooling in an ice-salt bath
  3. customfurther reacted for 2-3 hours
  4. customthe organic layer was collected
  5. washwashed with water (200 mL×2)
  6. dry with materiala saturated solution of sodium chloride (200 mL×1), and then dried overnight over anhydrous magnesium sulfate
  7. filtrationThe mixture was then filtered
  8. customevaporated under reduced pressure
  9. customto remove the solvent
  10. customrecrystallized in ethyl acetate

Sources & evidence

ORD record
ord-7257b2d4602b46a994bc0a277aa5b486
Source dataset
uspto-grants-2011_01
Patent number
US07872012B2

Reaction notes

Loading…