Lithium Hydroxide → HCID 70816461, compound

HRID 1843051Notes

Reaction equation

HRID 1843051 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[C:12]([CH2:13][NH:14][C:15](=[O:28])[NH:16][C:17]3[CH:26]=[CH:25][C:20]([C:21]([O:23]C)=[O:22])=[C:19]([F:27])[CH:18]=3)=[CH:11][C:10]([C:29]([F:32])([F:31])[F:30])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.[Li+].[OH-]>C1COCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[C:12]([CH2:13][NH:14][C:15](=[O:28])[NH:16][C:17]3[CH:26]=[CH:25][C:20]([C:21]([OH:23])=[O:22])=[C:19]([F:27])[CH:18]=3)=[CH:11][C:10]([C:29]([F:32])([F:30])[F:31])=[N:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 70816640methyl 4-(3-((1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)ureido)-2-fluorobenzoate

Product 1

HCID 70816461HCID 70816461, compoundYield 87.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

To a stirred solution of methyl 4-(3-((1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)ureido)-2-fluorobenzoate (120 mg, 0.25 mmol, 1.0 eq) in THF (10 mL) was added LiOH (21.4 mg, 0.51 mmol, 2.0 eq) dissolved in H2O (2 mL) at RT and stirred for 6 h at 45° C. The reaction mixture was concentrated, diluted with water (20 mL), brine (20 mL), the pH was adjusted to 4 with HCl (1N), and extracted with ethyl acetate (30 mL). The organic layer was washed with water (20 mL) brine (20 mL), dried over anhydrous Na2SO4 and evaporated under vacuum. The crude product was purified by CC using EtOAc/PE (7:3) to obtain 4-(3-((1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)ureido)-2-fluorobenzoic acid (100 mg; 85%) as a yellow solid (TLC: EtOAc/PE (7:3); Rf: 0.2).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with water (20 mL), brine (20 mL)
  3. extractionextracted with ethyl acetate (30 mL)
  4. washThe organic layer was washed with water (20 mL) brine (20 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. customevaporated under vacuum
  7. customThe crude product was purified by CC

Sources & evidence

ORD record
ord-5bda3e75a0344e1ea4018895a43bd7b3
Source dataset
uspto-grants-2015_02
Patent number
US08946204B2

Reaction notes

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