p-Toluenesulfonic acid monohydrate → HCID 178462432, compound

HRID 1936841Notes

Reaction equation

HRID 1936841 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1/[CH:10]=[CH:11]/[CH:12]=[CH:13]/[CH:14]=[O:15])[C:5]#[N:6].[F:16][C:17]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=1[C@:24]([OH:39])([C@H:31]([S:33][CH:34]([CH2:37]O)[CH2:35][OH:36])[CH3:32])[CH2:25][N:26]1[CH:30]=[N:29][CH:28]=[N:27]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>O1CCCC1>[C:5]([C:4]1[CH:7]=[CH:8][C:9](/[CH:10]=[CH:11]/[CH:12]=[CH:13]/[C@H:14]2[O:36][CH2:35][C@H:34]([S:33][C@H:31]([CH3:32])[C@:24]([C:18]3[CH:19]=[CH:20][C:21]([F:23])=[CH:22][C:17]=3[F:16])([OH:39])[CH2:25][N:26]3[CH:30]=[N:29][CH:28]=[N:27]3)[CH2:37][O:15]2)=[C:2]([F:1])[CH:3]=1)#[N:6]

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 102198523-Fluoro-4-[(1E,3E)-5-oxo-1,3-pentadienyl]benzonitrileHCID 10594623(2R,3R)-2-(2,4-difluorophenyl)-3-[[1-(hydroxymethyl)-2-hydroxyethyl]-thio]-1-(1H-1,2,4-triazol-1-yl)-2-butanol

Product 1

HCID 178462432HCID 178462432, compoundYield 74.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 4.63 g (23.0 mmol) of 3-fluoro-4-[(1E,3E)-5-oxo-1,3-pentadienyl]benzonitrile [produced as described in Step 1(ii) above], 8.73 g (24.3 mmol of (2R,3R)-2-(2,4-difluorophenyl)-3-[[1-(hydroxymethyl)-2-hydroxyethyl]thio]-1-(1H-1,2,4-triazol-1-yl)-2-butanol [produced as described in Japanese Patent Application (Kokai) Hei 8-333350)], 5.07 g (26.7 mmol) of p-toluenesulfonic acid monohydrate and 200 ml of anhydrous tetrahydrofuran was allowed to stand at ambient temperature for 30 minutes. At the end of this time, the reaction mixture was concentrated using a rotary evaporator and dried in vacuo. The resulting residue was dissolved in 150 ml of anhydrous tetrahydrofuran and the resulting mixture was then evaporated to dryness in vacuo using a rotary evaporator. This procedure was repeated twice more. A solution of the resulting residue in 150 ml of anhydrous tetrahydrofuran was poured into a saturated aqueous sodium hydrogen carbonate solution with stirring. The product was then extracted with ethyl acetate and the organic layer was washed with aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residual oil was purified by chromatography on a silica gel (500 g) column using a 2:1 mixture of ethyl acetate and hexane as the eluant to give 9.35 g (yield 74%) of the title compound as a yellow amorphous solid.

Workup

  1. customproduced
  2. concentrationAt the end of this time, the reaction mixture was concentrated
  3. customa rotary evaporator
  4. customdried in vacuo
  5. dissolutionThe resulting residue was dissolved in 150 ml of anhydrous tetrahydrofuran
  6. customthe resulting mixture was then evaporated to dryness in vacuo
  7. customa rotary evaporator
  8. additionA solution of the resulting residue in 150 ml of anhydrous tetrahydrofuran was poured into a saturated aqueous sodium hydrogen carbonate solution
  9. extractionThe product was then extracted with ethyl acetate
  10. washthe organic layer was washed with aqueous sodium chloride solution
  11. dry with materialdried over anhydrous magnesium sulfate
  12. concentrationconcentrated under reduced pressure
  13. customThe residual oil was purified by chromatography on a silica gel (500 g) column
  14. additiona 2:1 mixture of ethyl acetate and hexane as the eluant

Sources & evidence

ORD record
ord-006d3ff785bf4469aa05c731cb4ec9a8
Source dataset
uspto-grants-2002_05
Patent number
US06391903B1

Reaction notes

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