Water → 2-{8-(3,4-Difluorobenzyl)-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-8-yl}propan-2-ol

HRID 71120Notes

Reaction equation

HRID 71120 reaction equation
[CH3:1][Mg]Br.[F:4][C:5]1[CH:6]=[C:7]([CH:37]=[CH:38][C:39]=1[F:40])[CH2:8][C:9]1(C(OCC)=O)[CH2:14][CH2:13][CH2:12][N:11]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:10]12.[Cl-].[NH4+].O.[CH2:44]1[CH2:48][O:47]CC1>>[F:4][C:5]1[CH:6]=[C:7]([CH:37]=[CH:38][C:39]=1[F:40])[CH2:8][C:9]1([C:48]([OH:47])([CH3:44])[CH3:1])[CH2:14][CH2:13][CH2:12][N:11]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:10]12

Participants

6

Reactant 5

HCID 962WaterHCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 66603940Ethyl 8-(3,4-difluorobenzyl)-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-8-carboxylateHCID 178418573HCID 178418573, compound2×

Product 1

HCID 666039422-{8-(3,4-Difluorobenzyl)-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-8-yl}propan-2-ol

Procedure

Methylmagnesium bromide (12% THF solution, 13 mL) was added to a mixture of ethyl 8-(3,4-difluorobenzyl)-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-8-carboxylate (1.60 g) in THF (16 mL) under ice-cooling. The reaction mixture was stirred under ice-cooling for 1 hr, and methylmagnesium bromide (12% THF solution, 13 mL) was added under ice-cooling. The reaction mixture was stirred under ice-cooling for 1 hr, saturated aqueous ammonium chloride solution and water were added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane) to give the title compound (740 mg).

Workup

  1. temperaturecooling
  2. temperaturecooling for 1 hr
  3. temperaturecooling
  4. stirringThe reaction mixture was stirred under ice-
  5. temperaturecooling for 1 hr
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe extract was washed with saturated brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. customthe solvent was evaporated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane)

Sources & evidence

ORD record
ord-01a2745f3d1b4ead87e11d9d89ec4fc6
Source dataset
uspto-grants-2014_09
Patent number
US08822699B2

Reaction notes

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