Triethylamine → (2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)butan-2-yl methanesulfonate

HRID 1654201Notes

Reaction equation

HRID 1654201 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]([OH:19])([C@H:16]([OH:18])[CH3:17])[CH2:10][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1.C(N(CC)CC)C.[CH3:27][S:28](Cl)(=[O:30])=[O:29]>C(OCC)(=O)C.ClCCl>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]([OH:19])([C@H:16]([O:18][S:28]([CH3:27])(=[O:30])=[O:29])[CH3:17])[CH2:10][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 10286074(2R,3R)-2-(2,4-Difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2,3-butanediol

Product 1

HCID 14706441(2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)butan-2-yl methanesulfonate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

In a mixture of ethyl acetate (40 ml) and dichloromethane (10 ml) was dissolved (2R,3R)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2,3-butanediol (1.25 g). To the solution were added, under ice-cooling, triethylamine (0.84 ml) and methanesulfonyl chloride (0.48 ml), which was stirred for 30 minutes at room temperature. To the reaction mixture was added ethyl acetate (50 ml), which was washed with water, dried (anhydrous magnesium sulfate) and concentrated to give (2R,3R)-2-(2,4-difluorophenyl)-3-methanesulfonyloxy-1-(1H-1,2,4-triazol-1-yl)-2-butanol as an oily product. The product was dissolved in methanol (40 ml), to which was added a 28% methanol solution of sodium methylate (1.16 ml) under ice-cooling. The mixture was stirred for 30 minutes at room temperature. The reaction mixture was concentrated under reduced pressure to a volume of about 10 ml. To the concentrate was added ethyl acetate (100 ml), and the mixture was washed with water, then dried (anhydrous magnesium sulfate), followed by distilling off the solvent under reduced pressure. The residue was purified by means of a silica gel chromatography (eluent: ethyl acetate-dichloromethane=4:1), which was then recrystallized from a mixture of ethyl acetate and hexane to afford (2R,3S)-2-(2,4-difluorophenyl)-3-methyl-2-[(1H-1,2,4-triazol-1-yl)methyl]oxirane (520 mg) as colorless needles. m.p. 89°-90° C. [α]D23 =-8.3° (c=1.0 in MeOH)

Workup

  1. additionTo the solution were added, under ice-
  2. temperaturecooling
  3. washwas washed with water
  4. dry with materialdried (anhydrous magnesium sulfate)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-698cf200ea9043e6a3ba6e87875f91cd
Source dataset
uspto-grants-1995_04
Patent number
US05405861

Reaction notes

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