Lithium hydroxide, monohydrate → 3-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxylic acid

HRID 337014ノート

反応式

HRID 337014 の反応式
C[O:2][C:3]([C:5]1[S:6][C:7]([C:13]2[CH2:17][C:16]([C:22]3[CH:27]=[C:26]([Cl:28])[C:25]([F:29])=[C:24]([Cl:30])[CH:23]=3)([C:18]([F:21])([F:20])[F:19])[O:15][N:14]=2)=[C:8]2[CH2:12][CH2:11][CH2:10][C:9]=12)=[O:4].O[Li].O>O.C1COCC1>[Cl:30][C:24]1[CH:23]=[C:22]([C:16]2([C:18]([F:20])([F:21])[F:19])[O:15][N:14]=[C:13]([C:7]3[S:6][C:5]([C:3]([OH:4])=[O:2])=[C:9]4[CH2:10][CH2:11][CH2:12][C:8]=34)[CH2:17]2)[CH:27]=[C:26]([Cl:28])[C:25]=1[F:29]

参加物

5

反応物 2

HCID 168937Lithium hydroxide, monohydrateHCID 71472643Methyl 3-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxylate

生成物 1

HCID 714716353-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxylic acid

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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-carboxylic acid methyl ester (26 g, 54.1 mmol) and LiOH—H2O (4.54 g, 0.108 mmol) in water (200 mL) and THF (400 mL) at 50° C. for 0.5 hour. After removal of organic solvent under vacuum, dilute the residue with ice water (100 mL). Acidify the aqueous mixture with conc. HCl to pH=1, and extract the resultant mixture with EtOAc (200 mL×3). Purify the residue by silica gel chromatograph (EtOAc:MeOH 6:1) 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-carboxylic acid as a white solid (23 g, 91.7% for 2 steps). MS (m/z): 468 (M+1).

後処理

  1. customAfter removal of organic solvent under vacuum
  2. additiondilute the residue with ice water (100 mL)
  3. extractionextract the resultant mixture with EtOAc (200 mL×3)
  4. customPurify the residue by silica gel chromatograph (EtOAc:MeOH 6:1)

出典と根拠

ORDレコード
ord-f4ed50beb56440dca4adcad0d87520fa
出典データセット
uspto-grants-2014_11
特許番号
US08889710B2

反応ノート

読み込み中…