Potassium Carbonate → p-Toluenesulfonate

HRID 1857368Notes

Reaction equation

HRID 1857368 reaction equation
[S:1]([O:11][C@@H](O)C(O)C)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].[Cl:17][C:18]1[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:19]=1[C:25](=[O:32])[CH2:26][N:27]1[CH:31]=[N:30][CH:29]=[N:28]1.OS(C(F)(F)F)(=O)=O.C([O-])([O-])=O.[K+].[K+].[S:47]([O:57][C@H:58](O)[CH:59]([OH:61])[CH3:60])([C:50]1[CH:56]=[CH:55][C:53]([CH3:54])=[CH:52][CH:51]=1)(=[O:49])=[O:48]>C1(C)C=CC=CC=1.C(OCC)(=O)C.O.CO.CC#N>[S:1]([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)([OH:11])(=[O:3])=[O:2].[Cl:17][C:18]1[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:19]=1[C@:25]1([CH2:26][N:27]2[CH:31]=[N:30][CH:29]=[N:28]2)[O:61][C@H:59]([CH2:58][O:57][S:47]([C:50]2[CH:51]=[CH:52][C:53]([CH3:54])=[CH:55][CH:56]=2)(=[O:49])=[O:48])[CH2:60][O:32]1.[S:1]([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)([O-:11])(=[O:3])=[O:2]

Participants

12

Reactant 5

HCID 11430Potassium CarbonateHCID 62406Trifluoromethanesulfonic acidHCID 7393741-(2,4-Dichlorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethanone2×HCID 86756016HCID 86756016, compoundHCID 86756017HCID 86756017, compound

Product 2

HCID 85570p-ToluenesulfonateHCID 86756015HCID 86756015, compound

Reagents, catalysts & solvents 5

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 1140TolueneSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
5 °C

Procedure

(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-4-tosyloxymethyl-1,3-dioxolane tosylate DTTT (23 tosylate salt) is prepared as follows: A suspension of (R)-tosyloxy-1,2-propanediol (10.0 g, 40 mmol) and 1-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-yl) ethanone (10.0 g, 39 mmol) in toluene (50 mL) is cooled to 5° C. Triflic acid (15 mL, 4 eq) is slowly added so that the temperature stays below 15° C. After complete addition the reaction mixture (2 phases) is stirred at 25° C. for 60 h. The mixture is diluted with ethyl acetate (EtOAc) (200 mL) and slowly dropped into a solution of K2CO3 (50 g) in water (400 mL) at 5° C. The organic layer is separated and the aqueous layer washed with EtOAc (150 mL). The combined organic extracts are dried over Na2SO4 (10 g) and filtered. A solution of toluenesulfonic acid (TsOH) (7.6 g monohydrate in EtOAc (50 mL) is slowly added at 25° C. The white solid product is filtered after 30 min, washed and dried to give cis DTTT containing 5% trans. Two crystallyzations from CH3CN (400 mL) gives 13.5 g pure (2R,4S)-DTTT (50% yield); [a]D25 =+16.6° (c=1, MeOH); ee=99.6%. The 2S,4R isomer is prepared in analogous fashion from (S)-tosyloxy-1,2-propanediol (14.8 g, 60 mmol) and 1-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-yl) ethanone in (44% yield); [α]D25 =-16.6° (c=1, MeOH) ee=99.6%

Workup

  1. customstays below 15° C
  2. additionAfter complete addition the reaction mixture (2 phases)
  3. customThe organic layer is separated
  4. washthe aqueous layer washed with EtOAc (150 mL)
  5. dry with materialThe combined organic extracts are dried over Na2SO4 (10 g)
  6. filtrationfiltered
  7. additionA solution of toluenesulfonic acid (TsOH) (7.6 g monohydrate in EtOAc (50 mL) is slowly added at 25° C
  8. filtrationThe white solid product is filtered after 30 min
  9. washwashed
  10. customdried
  11. customto give cis DTTT
  12. additioncontaining 5% trans

Sources & evidence

ORD record
ord-3ca258ccebd74691b2617ec5ec083ad6
Source dataset
uspto-grants-2000_11
Patent number
US06147077

Reaction notes

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