Formaldehyde → (6RS,8RS)-8-(3,4-difluorophenyl)-8-(hydroxymethyl)-3-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-ol

HRID 71107Notes

Reaction equation

HRID 71107 reaction equation
[Si]([O:8][CH:9]1[CH2:14][N:13]2[C:15]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4[O:28][C:27]([CH3:29])=[N:26][CH:25]=4)=[C:20]([O:30][CH3:31])[CH:19]=3)=[N:16][N:17]=[C:12]2[CH:11]([C:32]2[CH:37]=[CH:36][C:35]([F:38])=[C:34]([F:39])[CH:33]=2)[CH2:10]1)(C(C)(C)C)(C)C.[H-].[Na+].[CH2:42]=[O:43].O>CN(C=O)C>[F:39][C:34]1[CH:33]=[C:32]([C:11]2([CH2:42][OH:43])[CH2:10][CH:9]([OH:8])[CH2:14][N:13]3[C:15]([C:18]4[CH:23]=[CH:22][C:21]([C:24]5[O:28][C:27]([CH3:29])=[N:26][CH:25]=5)=[C:20]([O:30][CH3:31])[CH:19]=4)=[N:16][N:17]=[C:12]23)[CH:37]=[CH:36][C:35]=1[F:38]

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 962WaterHCID 24758Sodium hydrideHCID 66607531HCID 66607531, compound

Product 1

HCID 66604124(6RS,8RS)-8-(3,4-difluorophenyl)-8-(hydroxymethyl)-3-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-olYield 86.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of (6RS,8SR)-6-{[tert-butyl(dimethyl)silyl]oxy}-8-(3,4-difluorophenyl)-3-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine (209 mg) in DMF (1.9 mL) was added sodium hydride (60%, 16.6 mg) at 0° C., and the mixture was stirred for 10 min. Paraformaldehyde (18.1 mg) was added to the reaction mixture, and the mixture was stirred at room temperature for 1 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. To a mixture of the residue in THF (1.9 mL) was added TBAF (1M THF solution, 0.756 mL), and the mixture was stirred at room temperature for 15 min. Saturated aqueous sodium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was washed with ethyl acetate to give the title compound (154 mg).

Workup

  1. stirringthe mixture was stirred at room temperature for 1 hr
  2. extractionthe mixture was extracted with ethyl acetate
  3. dry with materialThe extract was dried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. additionTo a mixture of the residue in THF (1.9 mL)
  6. additionwas added TBAF (1M THF solution, 0.756 mL)
  7. stirringthe mixture was stirred at room temperature for 15 min
  8. additionSaturated aqueous sodium chloride solution was added to the reaction mixture
  9. extractionthe mixture was extracted with ethyl acetate
  10. dry with materialThe extract was dried over anhydrous magnesium sulfate
  11. customthe solvent was evaporated under reduced pressure
  12. washThe residue was washed with ethyl acetate

Sources & evidence

ORD record
ord-f3e20cf34fa644ca9992c6122aabe79a
Source dataset
uspto-grants-2014_09
Patent number
US08822699B2

Reaction notes

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