Dimethylformamide → 2,5-Anhydro-1,3,4-trideoxy-2-C-(2,4-difluorophenyl)-4-(hydroxymethyl)-1-(1H-1,2,4-triazol-1-yl)-D-threo-pentitol

HRID 512807Notes

Reaction equation

HRID 512807 reaction equation
CC(C)([O-])C.[Na+].CN(C)C=O.[NH:12]1[CH:16]=[N:15][CH:14]=[N:13]1.[F:17][C:18]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=1[C@:25]1([CH2:32]I)[O:29][CH2:28][C@@H:27]([CH2:30][OH:31])[CH2:26]1>CN(C)C1C=CN=CC=1.ClCCl.O>[N:12]1([CH2:32][C@@:25]2([C:19]3[CH:20]=[CH:21][C:22]([F:24])=[CH:23][C:18]=3[F:17])[O:29][CH2:28][C@@H:27]([CH2:30][OH:31])[CH2:26]2)[CH:16]=[N:15][CH:14]=[N:13]1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 92571H-1,2,4-TriazoleHCID 15238252(3R-cis)-5-(2,4-difluorophenyl)tetrahydro-5-(iodomethyl)-3-furanmethanolHCID 23676156Sodium t-butoxide

Product 1

HCID 109243912,5-Anhydro-1,3,4-trideoxy-2-C-(2,4-difluorophenyl)-4-(hydroxymethyl)-1-(1H-1,2,4-triazol-1-yl)-D-threo-pentitol

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
105 °C

Procedure

Added 4-dimethylaminopyridine (8.61 g) and sodium tertiary butoxide (339 g) to a mixture of dimethylformamide (2500 ml) and 1,2,4-triazole (243.6 g) and stirred the reaction mixture for 30-45 minutes at 25-35° C. ((3R,5R)-5-(2,4-difluorophenyl)-5-(iodomethyl)tetrahydrofuran-3-yl)methanol compound of formula-8 (250 g) was added to the reaction mixture. The reaction mixture was heated to 100-110° C. and stirred for 18 hours at the same temperature. After completion of the reaction, the reaction mixture was cooled to 25-35° C. and then poured into water. Added dichloromethane to the reaction mixture. Both organic and aqueous layers were separated and the aqueous layer was extracted with dichloro methane. The combined dichloromethane layers were extracted with 50% aqueous HCl and separating both the aqueous and organic layers then pH of the aq. layer was adjusted to 8-9 with 50% aqueous sodium hydroxide. Both organic and aqueous layers were separated and the aqueous layer was extracted with ethyl acetate. The ethyl acetate layer was washed with water followed by sodium chloride solution and then distilled to get title compound as a residue. The obtained residue containing the title compound of formula-9 was taken to next step without isolation.

Workup

  1. additionwas added to the reaction mixture
  2. customAfter completion of the reaction
  3. temperaturethe reaction mixture was cooled to 25-35° C.
  4. customBoth organic and aqueous layers were separated
  5. extractionthe aqueous layer was extracted with dichloro methane
  6. extractionThe combined dichloromethane layers were extracted with 50% aqueous HCl
  7. customseparating both the aqueous and organic layers
  8. customBoth organic and aqueous layers were separated
  9. extractionthe aqueous layer was extracted with ethyl acetate
  10. washThe ethyl acetate layer was washed with water
  11. distillationdistilled

Sources & evidence

ORD record
ord-6026fed403084c43af9bef8c1c71cbdd
Source dataset
uspto-grants-2015_08
Patent number
US09102664B2

Reaction notes

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