Hydrochloric Acid → 2-(2,3-dihydro-1H-indol-1-yl)-4-[(4-fluorobenzyl)oxy]-5-pyrimidinecarboxylic acid

HRID 7433

反応式

HRID 7433 の反応式
[N:1]1([C:10]2[N:15]=[C:14]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[C:13]([C:25]([O:27]CC)=[O:26])=[CH:12][N:11]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.[OH-].[Na+].O1CCCC1.Cl>C(O)C>[N:1]1([C:10]2[N:15]=[C:14]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[C:13]([C:25]([OH:27])=[O:26])=[CH:12][N:11]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 21990499ethyl 2-(2,3-dihydro-1H-indol-1-yl)-4-[(4-fluorobenzyl)oxy]-5-pyrimidinecarboxylate

生成物 1

HCID 219904812-(2,3-dihydro-1H-indol-1-yl)-4-[(4-fluorobenzyl)oxy]-5-pyrimidinecarboxylic acid収率 101.1%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

実験手順

To a suspension of ethyl 2-(2,3-dihydro-1H-indol-1-yl)-4-[(4-fluorobenzyl)oxy]-5-pyrimidinecarboxylate (5.0 g, 13 mmol) in ethanol (25 mL) were added 10% aqueous sodium hydroxide solution (15 mL) and tetrahydrofuran (15 mL) and the mixture was heated under reflux for 30 min. The reaction mixture was allowed to cool to room temperature and 1N hydrochloric acid was added to adjust the reaction mixture to pH 5. The precipitated crystals were collected by filtration, washed several times with water, dried with heating under vacuum to give 2-(2,3-dihydro-1H-indol-1-yl)-4-[(4-fluorobenzyl)oxy]-5-pyrimidinecarboxylic acid (4.8 g, 100%) as crystals. To the obtained suspension of the obtained carboxylic acid (183 mg, 0.5 mmol), t-butyl glycine (89 mg, 0.53 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (102 mg, 0.53 mmol) in dichloromethane (2 mL) was added triethylamine (0.21 mL, 1.5 mmol) and the mixture was stirred at room temperature for 18 h. Water and ethyl acetate were added to the reaction mixture and the organic layer was concentrated under reduced pressure. The obtained residue was subjected to silica gel chromatography and eluted with ethyl acetate to give the title compound (210 mg, 88%).

後処理

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 30 min
  3. filtrationThe precipitated crystals were collected by filtration
  4. washwashed several times with water
  5. customdried
  6. temperaturewith heating under vacuum

出典と根拠

ORDレコード
ord-414b3cd795ae4514b86cda581bc75930
出典データセット
uspto-grants-2006_08
特許番号
US07087597B1

関連ノート

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