p-Toluenesulfonic acid monohydrate → HCID 178462432, compound

HRID 1937145Notes

Reaction equation

HRID 1937145 reaction equation
O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[F:13][C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][C:21]=1/[CH:22]=[CH:23]/[CH:24]=[CH:25]/[CH:26]=[O:27])[C:17]#[N:18].[F:28][C:29]1[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=1[C@:36]([OH:51])([C@H:43]([S:45][CH:46]([CH2:49]O)[CH2:47][OH:48])[CH3:44])[CH2:37][N:38]1[CH:42]=[N:41][CH:40]=[N:39]1>ClCCl>[C:17]([C:16]1[CH:19]=[CH:20][C:21](/[CH:22]=[CH:23]/[CH:24]=[CH:25]/[C@H:26]2[O:48][CH2:47][C@H:46]([S:45][C@H:43]([CH3:44])[C@:36]([C:30]3[CH:31]=[CH:32][C:33]([F:35])=[CH:34][C:29]=3[F:28])([OH:51])[CH2:37][N:38]3[CH:42]=[N:41][CH:40]=[N:39]3)[CH2:49][O:27]2)=[C:14]([F:13])[CH:15]=1)#[N:18]

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 69.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

791 mg (4.16 mmol) of p-toluenesulfonic acid monohydrate were added to a solution of 760 mg (3.77 mmol) of 3-fluoro-4-[(1E,3E)-5-oxo-1,3-pentadienyl]-benzonitrile [obtained as described in Example 1(ii) above] and 1.36 g (3.77 mmol) of (2R,3 R)-2-(2,4-difluorophenyl)-3-[[1-(hydroxymethyl)-2 -hydroxyethyl]thio]-1-(1H-1,2,4-triazol-1-yl)-2-butanol [prepared as described in Japanese Patent Application (Kokai) Hei 8-333350] in 13 ml of dichloromethane. The resulting mixture was concentrated using a rotary evaporator. 13 ml of dichloromethane and 13 g of 4A molecular sieves were added to the resulting residue and the mixture was then stirred at ambient temperature overnight. At the end of this time, an aqueous sodium hydrogen carbonate solution was added to the reaction mixture. The molecular sieves were removed by filtration and the filtrate was partitioned between ethyl acetate and water. The organic layer was dried and concentrated under reduced pressure. The resulting oil residue was purified by chromatography on a silica gel (20 a) column using a 1:1 mixture of ethyl acetate and hexane as the eluant to afford 1.42 g (yield 69%) of the title compound as an amorphous solid. The spectral data were identical to those of the title compound of Example 1.

Workup

  1. concentrationThe resulting mixture was concentrated
  2. customa rotary evaporator
  3. addition13 ml of dichloromethane and 13 g of 4A molecular sieves were added to the resulting residue
  4. additionAt the end of this time, an aqueous sodium hydrogen carbonate solution was added to the reaction mixture
  5. customThe molecular sieves were removed by filtration
  6. customthe filtrate was partitioned between ethyl acetate and water
  7. customThe organic layer was dried
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting oil residue was purified by chromatography on a silica gel (20 a) column
  10. additiona 1:1 mixture of ethyl acetate and hexane as the eluant

Sources & evidence

ORD record
ord-f44447a7c78e4e899053145b52943302
Source dataset
uspto-grants-2002_05
Patent number
US06392082B1

Reaction notes

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