Lithium hydroxide, monohydrate → 2-(3-(5-(3,5-Dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-4,5,6,7-tetrahydrobenzo[c]thiophene-1-carboxamido)acetic acid

HRID 336993Notes

Reaction equation

HRID 336993 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:31]([F:34])([F:33])[F:32])[O:13][N:12]=[C:11]([C:14]3[S:18][C:17]([C:19]([NH:21][CH2:22][C:23]([O:25]C)=[O:24])=[O:20])=[C:16]4[CH2:27][CH2:28][CH2:29][CH2:30][C:15]=34)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.O[Li].O>CO.O>[Cl:8][C:6]1[CH:5]=[C:4]([C:9]2([C:31]([F:32])([F:34])[F:33])[O:13][N:12]=[C:11]([C:14]3[S:18][C:17]([C:19]([NH:21][CH2:22][C:23]([OH:25])=[O:24])=[O:20])=[C:16]4[CH2:27][CH2:28][CH2:29][CH2:30][C:15]=34)[CH2:10]2)[CH:3]=[C:2]([Cl:1])[CH:7]=1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 71467510Methyl 2-(3-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-4,5,6,7-tetrahydrobenzo[c]thiophene-1-carboxamido)acetate

Product 1

HCID 714688182-(3-(5-(3,5-Dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-4,5,6,7-tetrahydrobenzo[c]thiophene-1-carboxamido)acetic acidYield 82%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Stir a mixture of methyl 2-(3-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-4,5,6,7-tetrahydrobenzo[c]thiophene-1-carboxamido)acetate (534 mg, 1.0 mmol) and LiOH—H2O (168 mg, 4.0 mmol) in MeOH (20 mL) and water (5 mL) at room temperature for overnight. After removal of organic solvent under vacuum, dilute the residue with ice water (10 mL). Acidify the aqueous mixture with conc. HCl to pH=1, and extract the resultant mixture with EtOAc (15 mL×3). The combined organic layers are washed brine, dried over anhydrous Na2SO4 and concentrated under vacuum. Purify the residue by silica gel chromatograph (PE:EtOAc 1:1) to afford 2-(3-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-4,5,6,7-tetrahydrobenzo[c]thiophene-1-carboxamido)acetic acid as a pale yellow solid (427 mg, 82.0%). MS (m/z): 521 (M+1).

Workup

  1. customAfter removal of organic solvent under vacuum
  2. additiondilute the residue with ice water (10 mL)
  3. extractionextract the resultant mixture with EtOAc (15 mL×3)
  4. washThe combined organic layers are washed brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated under vacuum
  7. customPurify the residue by silica gel chromatograph (PE:EtOAc 1:1)

Sources & evidence

ORD record
ord-b612348aad0b4052b6e28a4bc7e78487
Source dataset
uspto-grants-2014_11
Patent number
US08889710B2

Reaction notes

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