Hydrochloric Acid → HCID 53495669, compound

HRID 77180Notes

Reaction equation

HRID 77180 reaction equation
[OH:1][CH:2]([C:14]1[CH:19]=[CH:18][C:17]([C:20]2[N:24]=[C:23]([C:25]3[CH:26]=[N:27][N:28]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)[C:29]=3[C:30]([F:33])([F:32])[F:31])[O:22][N:21]=2)=[CH:16][CH:15]=1)[C:3]([NH:5][CH2:6][C:7]([O:9]C(C)(C)C)=[O:8])=[O:4].[Li+].[OH-].Cl>C1COCC1.CO>[OH:1][CH:2]([C:14]1[CH:19]=[CH:18][C:17]([C:20]2[N:24]=[C:23]([C:25]3[CH:26]=[N:27][N:28]([C:34]4[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=4)[C:29]=3[C:30]([F:31])([F:32])[F:33])[O:22][N:21]=2)=[CH:16][CH:15]=1)[C:3]([NH:5][CH2:6][C:7]([OH:9])=[O:8])=[O:4]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium Hydroxide2×HCID 53495667(R/S)-tert-butyl 2-(2-hydroxy-2-(4-(5-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamido)acetate

Product 1

HCID 53495669HCID 53495669, compoundYield 52.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

(R/S)-tert-Butyl 2-(2-hydroxy-2-(4-(5-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamido)acetate (Example 56, 30 mg, 0.055 mmol) was dissolved in THF (3 mL) and MeOH (1.50 mL). Next, LiOH (2.64 mg, 0.110 mmol) was added. After 20 min, additional LiOH (2.64 mg, 0.110 mmol) was added. After another 20 min, 1N HCl was used to adjust the pH to 4-5. The reaction mixture was concentrated. EtOAc was added and the resulting mixture was filtered. The filtrate was concentrated to provide (R/S)-2-(2-hydroxy-2-(4-(5-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamido)acetic acid (15 mg, 0.029 mmol, 52.2% yield): LCMS=488.2 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.47 (1 H, s), 8.13 (2 H, d, J=8.35 Hz), 7.53-7.75 (7 H, m), 5.17 (1 H, s), 3.99 (2 H, s); HPLC peak RT=7.1 min (Method A).

Workup

  1. waitAfter another 20 min
  2. concentrationThe reaction mixture was concentrated
  3. additionEtOAc was added
  4. filtrationthe resulting mixture was filtered
  5. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-4dd38ed4be1e4b0cba70ac1c700aac76
Source dataset
uspto-grants-2014_09
Patent number
US08835470B2

Reaction notes

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