Lithium hydroxide, monohydrate → ({3-[5-(3,5-Dichloro-4-fluoro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carbonyl}-amino)-acetic acid

HRID 337016Notes

Reaction equation

HRID 337016 reaction equation
C[O:2][C:3](=[O:34])[CH2:4][NH:5][C:6]([C:8]1[S:9][C:10]([C:16]2[CH2:20][C:19]([C:25]3[CH:30]=[C:29]([Cl:31])[C:28]([F:32])=[C:27]([Cl:33])[CH:26]=3)([C:21]([F:24])([F:23])[F:22])[O:18][N:17]=2)=[C:11]2[CH2:15][CH2:14][CH2:13][C:12]=12)=[O:7].O[Li].O>C1COCC1.O>[Cl:31][C:29]1[CH:30]=[C:25]([C:19]2([C:21]([F:22])([F:24])[F:23])[O:18][N:17]=[C:16]([C:10]3[S:9][C:8]([C:6]([NH:5][CH2:4][C:3]([OH:34])=[O:2])=[O:7])=[C:12]4[CH2:13][CH2:14][CH2:15][C:11]=34)[CH2:20]2)[CH:26]=[C:27]([Cl:33])[C:28]=1[F:32]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86693751({3-[5-(3,5-Dichloro-4-fluoro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carbonyl}-amino)-acetic acid methyl ester

Product 1

HCID 86693752({3-[5-(3,5-Dichloro-4-fluoro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carbonyl}-amino)-acetic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Stir a mixture of ({3-[5-(3,5-Dichloro-4-fluoro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carbonyl}-amino)-acetic acid methyl ester (11 g, 18.6 mmol) and LiOH—H2O (1.56 g, 37.2 mmol) in THF (100 mL) and water (50 mL) at room temperature for overnight. After being checked with TLC, the solvent is removed under vacuum, dilute the residue with water (50 mL). Acidify the aqueous mixture with 2M HCl to pH=3, and extract the resultant mixture with EtOAc (100 mL×3), the combined organic layer is washed with brine, dried over anhydrous Na2SO4 and concentrated under vacuum, the residue is purified by silica gel chromatograph (PE:EtOAc 1:1) to afford ({3-[5-(3,5-Dichloro-4-fluoro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carbonyl}-amino)-acetic acid as a white solid (10.2 g, 90.7% for two steps). MS (m/z): 525 (M+1).

Workup

  1. customthe solvent is removed under vacuum
  2. additiondilute the residue with water (50 mL)
  3. extractionextract the resultant mixture with EtOAc (100 mL×3)
  4. washthe combined organic layer is washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated under vacuum
  7. customthe residue is purified by silica gel chromatograph (PE:EtOAc 1:1)

Sources & evidence

ORD record
ord-9832d1b89d2a44b790c3bd82977eaa63
Source dataset
uspto-grants-2014_11
Patent number
US08889710B2

Reaction notes

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