Hydrochloric Acid → 2-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]thieno[2,3-b]pyridine-5-carboxylic acid

HRID 337001Notes

Reaction equation

HRID 337001 reaction equation
O[Li].O.[Cl:4][C:5]1[CH:6]=[C:7]([C:12]2([C:30]([F:33])([F:32])[F:31])[O:16][N:15]=[C:14]([C:17]3[S:29][C:20]4=[N:21][CH:22]=[C:23]([C:25]([O:27]C)=[O:26])[CH:24]=[C:19]4[CH:18]=3)[CH2:13]2)[CH:8]=[C:9]([Cl:11])[CH:10]=1.Cl>O.C1COCC1>[Cl:11][C:9]1[CH:8]=[C:7]([C:12]2([C:30]([F:32])([F:31])[F:33])[O:16][N:15]=[C:14]([C:17]3[S:29][C:20]4=[N:21][CH:22]=[C:23]([C:25]([OH:27])=[O:26])[CH:24]=[C:19]4[CH:18]=3)[CH2:13]2)[CH:6]=[C:5]([Cl:4])[CH:10]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 71469063Methyl 2-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)thieno[2,3-b]pyri dine-5-carboxylate

Product 1

HCID 714691762-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]thieno[2,3-b]pyridine-5-carboxylic acidYield 73.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

Add a solution of LiOH—H2O (76 mg, 2 mmol) in water (0.5 mL) to a solution of methyl 2-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)thieno[2,3-b]pyridine-5-carboxylate (237 mg, 0.5 mmol) in THF (3 mL). Stir the mixture at temperature for 12 hours. After addition of 10 mL of water, acidify the mixture with concentrated HCl to PH=6˜7. Extract the resultant mixture with ethyl acetate (3×10 mL). The combined organic layers are washed brine, dried over anhydrous Na2SO4 and concentrated under vacuum to afford 2-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]thieno[2,3-b]pyridine-5-carboxylic acid as pale yellow solid (170 mg, 73.9%), which is used in next step without further purification. MS (m/z): 461 (M+1).

Workup

  1. extractionExtract the resultant mixture with ethyl acetate (3×10 mL)
  2. washThe combined organic layers are washed brine
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-df1c8871a1a847e0835e3aaf55a8f02b
Source dataset
uspto-grants-2014_11
Patent number
US08889710B2

Reaction notes

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