Hydrochloric Acid → 8-[5-(Trifluoromethyl)-5-(3,5-dichlorophenyl)-2-isoxazoline-3-yl]indolizine-5-carboxylic acid

HRID 1037083Notes

Reaction equation

HRID 1037083 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:28]([F:31])([F:30])[F:29])[O:13][N:12]=[C:11]([C:14]3[C:22]4[N:18]([CH:19]=[CH:20][CH:21]=4)[C:17]([C:23]([O:25]CC)=[O:24])=[CH:16][CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.[OH-].[Na+].Cl>O.CO>[Cl:8][C:6]1[CH:5]=[C:4]([C:9]2([C:28]([F:29])([F:31])[F:30])[O:13][N:12]=[C:11]([C:14]3[C:22]4[N:18]([CH:19]=[CH:20][CH:21]=4)[C:17]([C:23]([OH:25])=[O:24])=[CH:16][CH:15]=3)[CH2:10]2)[CH:3]=[C:2]([Cl:1])[CH:7]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 86685521Ethyl 8-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)indolizine-5-carboxylate

Product 1

HCID 866855228-[5-(Trifluoromethyl)-5-(3,5-dichlorophenyl)-2-isoxazoline-3-yl]indolizine-5-carboxylic acidYield 47.2%

Reagents, catalysts & solvents 1

HCID 22242641Methanol--water (1/1)Solvent

Procedure

A solution of ethyl 8-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)indolizine-5-carboxylate (50 mg, 0.11 mmol) and NaOH (21 mg, 0.55 mmol) in H2O-MeOH (1:1, 20 mL) was stirred at rt for 3 h. The mixture was acidified with 2 N HCl and extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by prep-TLC to give 8-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)indolizine-5-carboxylic acid (23 mg, yield 47%) as a yellow solid. MS: m/z=443.7 (M+1, ESI+).

Workup

  1. extractionextracted with ethyl acetate (3×20 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by prep-TLC

Sources & evidence

ORD record
ord-525ac6a8b01b45e48955f2510b39b26f
Source dataset
uspto-grants-2013_10
Patent number
US08546357B2

Reaction notes

Loading…