Tetrahydrofuran → 2-{3-[3-Methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-8-[4-(trifluoromethyl)phenoxy]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-8-yl}propan-2-ol

HRID 1398191Notes

Reaction equation

HRID 1398191 reaction equation
[CH3:1][Mg]Br.[CH3:4][O:5][C:6]1[CH:7]=[C:8]([C:18]2[N:22]3[CH2:23][CH2:24][CH2:25][C:26]([O:32][C:33]4[CH:38]=[CH:37][C:36]([C:39]([F:42])([F:41])[F:40])=[CH:35][CH:34]=4)(C(OCC)=O)[C:21]3=[N:20][N:19]=2)[CH:9]=[CH:10][C:11]=1[C:12]1[O:16][C:15]([CH3:17])=[N:14][CH:13]=1.[Cl-].[NH4+].[CH2:45]1[CH2:49][O:48]CC1>>[CH3:4][O:5][C:6]1[CH:7]=[C:8]([C:18]2[N:22]3[CH2:23][CH2:24][CH2:25][C:26]([C:49]([OH:48])([CH3:45])[CH3:1])([O:32][C:33]4[CH:38]=[CH:37][C:36]([C:39]([F:41])([F:42])[F:40])=[CH:35][CH:34]=4)[C:21]3=[N:20][N:19]=2)[CH:9]=[CH:10][C:11]=1[C:12]1[O:16][C:15]([CH3:17])=[N:14][CH:13]=1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 66607518Ethyl 3-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-8-[4-(trifluoromethyl)phenoxy]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-8-carboxylateHCID 178418573HCID 178418573, compound

Product 1

HCID 569295462-{3-[3-Methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-8-[4-(trifluoromethyl)phenoxy]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-8-yl}propan-2-ol

Procedure

Methylmagnesium bromide (1M THF solution, 4.75 ml) was added to a mixture of ethyl 3-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-8-[4-(trifluoromethyl)phenoxy]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-8-carboxylate (515 mg) in THF (7 mL) under ice-cooling, and the mixture was stirred for 1 hr. Saturated aqueous ammonium chloride solution was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by basic silica gel column chromatography (NH, ethyl acetate/hexane) to give the title compound (250 mg).

Workup

  1. temperaturecooling
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by basic silica gel column chromatography (NH, ethyl acetate/hexane)

Sources & evidence

ORD record
ord-4a715de152d844eeb45163af67e31492
Source dataset
uspto-grants-2014_12
Patent number
US08901309B2

Reaction notes

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