Water → 4-[5-(5-Chloro-6-isobutoxypyridin-3-yl)-1,2,4-oxadiazol-3-yl]-2-fluorobenzoic acid

HRID 219915Notes

Reaction equation

HRID 219915 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Cl:11][C:12]1[CH:13]=[C:14]([C:19]2[O:23][N:22]=[C:21]([C:24]3[CH:33]=[CH:32][C:27]([C:28]([O:30]C)=[O:29])=[C:26]([F:34])[CH:25]=3)[N:20]=2)[CH:15]=[N:16][C:17]=1Cl.[OH2:35]>CC(C)CO.C1COCC1.CCOC(C)=O>[Cl:11][C:12]1[CH:13]=[C:14]([C:19]2[O:23][N:22]=[C:21]([C:24]3[CH:33]=[CH:32][C:27]([C:28]([OH:30])=[O:29])=[C:26]([F:34])[CH:25]=3)[N:20]=2)[CH:15]=[N:16][C:17]=1[O:35][CH2:13][CH:14]([CH3:19])[CH3:15]

Participants

7

Reactant 3

HCID 962WaterHCID 2733832Lithium HexamethyldisilazideHCID 86645653Methyl 4-[5-(5,6-dichloropyridin-3-yl)-1,2,4-oxadiazol-3-yl]-2-fluorobenzoate

Product 1

HCID 252563804-[5-(5-Chloro-6-isobutoxypyridin-3-yl)-1,2,4-oxadiazol-3-yl]-2-fluorobenzoic acid

Reagents, catalysts & solvents 3

HCID 6560IsobutanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Lithium bis(trimethylsilyl)amide (700 μL; 1 M; 0.70 mmol) was added to a solution of methyl 4-[5-(5,6-dichloropyridin-3-yl)-1,2,4-oxadiazol-3-yl]-2-fluorobenzoate, obtained in step 1 (73.63 mg; 0.20 mmol) in 2-methyl-1-propanol (3 mL) and THF (2 mL). The resulting mixture was stirred at RT for 1 h. Water (500 uL) was added and the mixture was stirred at RT for 3 h, saponification was complete. The reaction mixture was then diluted with EtOAc and washed with HCl 1N, NaCl sat. solution and dried over magnesium sulfate. After evaporation of the solvents, the crude was purified by HPLC prep to afford the title compound as a slightly yellow powder. 1H NMR (DMSO-d6, 300 MHz) δ 8.94 (d, J=2.2 Hz, 1H), 8.60 (d, J=2.2 Hz, 1H), 8.08 (t, J=7.7 Hz, 1H), 8.01 (dd, J=8.1, 1.5 Hz, 1H), 7.94 (dd, J=11.1, 1.5 Hz, 1H), 4.27 (d, J=6.5 Hz, 2H), 2.16-2.07 (m, 1H), 1.01 (d, J=6.6 Hz, 6H). LC/MS (Method B): 390.3 (M−H)−, 392.2 (M+H)+. HPLC (Method A) Rt 5.49 min (Purity: 98.6%).

Workup

  1. stirringthe mixture was stirred at RT for 3 h
  2. washwashed with HCl 1N, NaCl sat. solution
  3. dry with materialdried over magnesium sulfate
  4. customAfter evaporation of the solvents
  5. customthe crude was purified by HPLC prep

Sources & evidence

ORD record
ord-7d264019e5964879a7ee08dc51b2d1fb
Source dataset
uspto-grants-2012_06
Patent number
US08202865B2

Reaction notes

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