Lithium Hydroxide → 1-(2-chlorophenyl)-5-(5-(3-(methylsulfonyl)phenyl)-1,3,4-oxadiazol-2-yl)-1H-pyrazole-3-carboxylic acid

HRID 877440Notes

Reaction equation

HRID 877440 reaction equation
C[C:2]1[C:3]([C:29]([OH:31])=[O:30])=[N:4][N:5]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[Cl:28])[C:6]=1[C:7]1[O:8][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([S:18]([CH3:21])(=[O:20])=[O:19])[CH:13]=2)=[N:10][N:11]=1.[OH-].[Li+]>C1COCC1.O>[Cl:28][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[N:5]1[C:6]([C:7]2[O:8][C:9]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([S:18]([CH3:21])(=[O:20])=[O:19])[CH:13]=3)=[N:10][N:11]=2)=[CH:2][C:3]([C:29]([OH:31])=[O:30])=[N:4]1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 117962551methyl 1-(2-chlorophenyl)-5-(5-(3-(methylsulfonyl)phenyl)-1,3,4-oxadiazol-2-yl)-1H-pyrazole-3-carboxylic acid

Product 1

HCID 897827431-(2-chlorophenyl)-5-(5-(3-(methylsulfonyl)phenyl)-1,3,4-oxadiazol-2-yl)-1H-pyrazole-3-carboxylic acidYield 32.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of compound 11 (100 mg, 0.21 mmol) in THF (4.0 mL) at room temperature, a solution of lithium hydroxide (44 mg, 1.05 mmol) in water (4.0 mL) was added and stirring continued for 2 h. On completion, solvent was removed, diluted with water (20 mL) and washed with ether (30 mL×3). The aqueous layer was acidified with 1N HCl and extracted with 10% methanol in dichloromethane (50 mL×3). Combined organic layer was washed brine, dried over sodium sulphate and concentrated. The crude product after ether and pentane washing furnished the title compound 12 (30 mg, 31%). LCMS: 445.10 (M+1)+; HPLC: 96.20% (@210 nm-370 nm) (Rf; 5.847; Method: Column: YMC ODS-A 150 mm×4.6 mm×5μ; Mobile Phase: A; 0.05% TFA in water/B; 0.05% TFA in acetonitrile; Inj. Vol: 10 μL, Col. Temp.: 30 OC; Flow rate: 1.4 mL/min.; Gradient: 5% B to 95% B in 8 min, Hold for 1.5 min, 9.51-12 min 5% B); 1H NMR (CDCl3, 400 MHz) δ 8.29 (s, 1H), 8.27 (d, 1H), 8.12 (d, 1H, J=7.6 Hz), 7.79 (s, 1H), 7.74 (t, 1H, J=7.6&7.2 Hz), 7.64-7.50 (m, 4H), 3.10 (s, 3H).

Workup

  1. customOn completion, solvent was removed
  2. additiondiluted with water (20 mL)
  3. washwashed with ether (30 mL×3)
  4. extractionextracted with 10% methanol in dichloromethane (50 mL×3)
  5. washCombined organic layer was washed brine
  6. dry with materialdried over sodium sulphate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-8a1d53cf9d10430790c3b09fdbdca118
Source dataset
uspto-grants-2015_03
Patent number
US08987318B2

Reaction notes

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