p-Toluenesulfonic acid monohydrate → (2R, 3R)-2-(2,4-difluorophenyl)-3-(4-methylenepiperidino)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol p-toluenesulfonate

HRID 53662Notes

Reaction equation

HRID 53662 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]1([CH2:13][N:14]2[CH:18]=[N:17][CH:16]=[N:15]2)[C@H:11]([CH3:12])[O:10]1.O.[C:20]1([CH3:30])[CH:25]=[CH:24][C:23]([S:26]([OH:29])(=[O:28])=O)=[CH:22][CH:21]=1.[CH2:31]=[C:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1>C(O)(C)C>[C:20]1([CH3:30])[CH:21]=[CH:22][C:23]([S:26]([O:10][C@@:9]([C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[F:1])([C@H:11]([N:35]2[CH2:36][CH2:37][C:32](=[CH2:31])[CH2:33][CH2:34]2)[CH3:12])[CH2:13][N:14]2[CH:18]=[N:17][CH:16]=[N:15]2)(=[O:28])=[O:29])=[CH:24][CH:25]=1

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 53146584-MethylenepiperidineHCID 101311911-((2-(2,4-Difluorophenyl)-3-methyloxiran-2-yl)methyl)-1H-1,2,4-triazole, (2R-cis)-

Product 1

HCID 88342129(2R, 3R)-2-(2,4-difluorophenyl)-3-(4-methylenepiperidino)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol p-toluenesulfonate

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

There was dissolved 17.59 g (70 mmol) of (2R,3S)-2-(2,4-difluorophenyl)-3-methyl-2-[(1H-1,2,4-triazole-1-yl)methyl]oxirane in 113 g of an aqueous solution of 4-methylenepiperidine (content: 61%) and the obtained solution was refluxed with heating at 90° C. for 21 hours. After the reaction, an excess of 4-methylenepiperidine was removed under reduced pressure, and the residue was dissolved in 140 ml of isopropyl alcohol and thereto was added 13.32 g (70 mmol) of p-toluenesulfonic acid monohydrate dissolved in 50 ml of isopropyl alcohol. The obtained mixture was allowed to stand for 1 hour at room temperature and overnight in a refrigerator, and then the precipitated crystal was separated by filtration and washed with 50 ml of isopropyl alcohol and dried to obtain 32.20 g of (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylenepiperidine-1-yl)-1-(1H-1,2,4-triazole-1-yl)butane-2-ol p-toluenesulfonate in a form of a crystal.

Workup

  1. temperaturethe obtained solution was refluxed
  2. customAfter the reaction
  3. customan excess of 4-methylenepiperidine was removed under reduced pressure
  4. dissolutionthe residue was dissolved in 140 ml of isopropyl alcohol
  5. customthe precipitated crystal was separated by filtration
  6. washwashed with 50 ml of isopropyl alcohol
  7. customdried

Sources & evidence

ORD record
ord-4f8e4265fae44906b5cb69ea516365bb
Source dataset
uspto-grants-1997_04
Patent number
US05620994

Reaction notes

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