Sodium Methoxide → HCID 178462386, compound

HRID 1250378Notes

Reaction equation

HRID 1250378 reaction equation
C[O-].[Na+].[F:4][C:5]1[C:10]([F:11])=[CH:9][CH:8]=[CH:7][C:6]=1[C@@:12]1([CH2:16][N:17]2[CH:21]=[N:20][CH:19]=[N:18]2)[C@H:14]([CH3:15])[O:13]1.C([S:25][C@@H:26]1[CH2:31][O:30][C@@H:29]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[O:28][CH2:27]1)(=O)C>CO.C(O)C>[F:4][C:5]1[C:10]([F:11])=[CH:9][CH:8]=[CH:7][C:6]=1[C@:12]([OH:13])([C@H:14]([S:25][C@@H:26]1[CH2:27][O:28][C@@H:29]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[O:30][CH2:31]1)[CH3:15])[CH2:16][N:17]1[CH:21]=[N:20][CH:19]=[N:18]1

Participants

6

Reactant 3

HCID 10942334Sodium MethoxideHCID 86757717(2R,3S)-2-(2,3-Difluorophenyl)-3-methyl-2-[(1H-1,2,4-triazol-1-yl)methyl]oxiraneHCID 178477153HCID 178477153, compound

Product 1

HCID 178462386HCID 178462386, compoundYield 6.6%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 887MethanolSolvent

Procedure

0.29 ml (1.4 mmol) of a 4.9 M solution of sodium methoxide in methanol were added to a solution of 1.77 g (7.1 mmol) of (2R,3S)-2-(2,3-difluorophenyl)-3-methyl-2-[(1H-1,2,4-triazol-1-yl)methyl]oxirane [prepared as described in Step 7(iv) above] and 2.20 g (9.2 mmol) of trans-5-(acetylthio)-2-phenyl-1,3-dioxane [prepared as described in Japanese Patent Application (Kokai) Hei 8-333350] in 20 ml of ethanol. The resulting mixture was then heated under reflux for 7 hours. After cooling the reaction mixture, it was partitioned between ethyl acetate and an aqueous ammonium chloride solution. The organic layer was washed with saturated aqueous sodium chloride solution and concentrated under reduced pressure to afford 3.65 g of the crude title compound. An aliquot (0.28 g) of the crude residue was purified by chromatography on a silica gel (15 g) column using a 2:5 mixture of ethyl acetate and hexane as eluent to afford 0.21 g of the title compound.

Workup

  1. temperatureThe resulting mixture was then heated
  2. temperatureunder reflux for 7 hours
  3. temperatureAfter cooling the reaction mixture, it
  4. customwas partitioned between ethyl acetate
  5. washThe organic layer was washed with saturated aqueous sodium chloride solution
  6. concentrationconcentrated under reduced pressure
  7. customto afford 3.65 g of the crude title compound
  8. customAn aliquot (0.28 g) of the crude residue was purified by chromatography on a silica gel (15 g) column
  9. additiona 2:5 mixture of ethyl acetate and hexane as eluent

Sources & evidence

ORD record
ord-6d7564fdaa5e4f9d82570d0803437bef
Source dataset
uspto-grants-2002_01
Patent number
US06337403B1

Reaction notes

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