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Citric Acid → 4,6-Difluoro-5-(4-(1-hydroxycyclobutyl)phenyl)-1H-indole-3-carboxylic acid

HRID 1054575
ノート
印刷プレビュー

反応式

HRID 1054575 の反応式
[F:1][C:2]1[C:10]([C:11]2[CH:16]=[CH:15][C:14]([C:17]3([OH:21])[CH2:20][CH2:19][CH2:18]3)=[CH:13][CH:12]=2)=[C:9]([F:22])[CH:8]=[C:7]2[C:3]=1[C:4]([CH:23]=[O:24])=[CH:5][NH:6]2.O.[OH:26]P([O-])(O)=O.[Na+].Cl([O-])=O.[Na+].CC(=CC)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CC#N.O.C(O)(C)(C)C>[F:1][C:2]1[C:10]([C:11]2[CH:12]=[CH:13][C:14]([C:17]3([OH:21])[CH2:18][CH2:19][CH2:20]3)=[CH:15][CH:16]=2)=[C:9]([F:22])[CH:8]=[C:7]2[C:3]=1[C:4]([C:23]([OH:26])=[O:24])=[CH:5][NH:6]2
参加物実験手順後処理出典と根拠反応ノート

参加物

9

反応物 5

HCID 311Citric AcidHCID 105532-Methyl-2-buteneHCID 516949Sodium Phosphate, Monobasic, MonohydrateHCID 23668197Sodium ChloriteHCID 866985794,6-Difluoro-5-(4-(1-hydroxycyclobutyl)phenyl)-1H-indole-3-carbaldehyde

生成物 1

HCID 717678334,6-Difluoro-5-(4-(1-hydroxycyclobutyl)phenyl)-1H-indole-3-carboxylic acid
収率 24.9%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6342Acetonitrile溶媒HCID 6386tert-Butanol溶媒

実験手順

To a solution of 4,6-difluoro-5-[4-(1-hydroxy-cyclobutyl)-phenyl]-1H-indole-3-carbaldehyde (37.0 mg, 0.11 mmol) in a mixture of MeCN (2 mL), tert-butanol (1 mL) and water (2 mL) was added sodium phosphate monobasic hydrate (214.0 mg, 1.55 mmol), sodium chlorite (114.0 mg, 1.26 mmol) and 2-methyl-2-butene (1.0 mL, 6.85 mmol). The reaction mixture was stirred at room temperature for 24 hours, acidified with 1 N aqueous citric acid solution (1 mL) and extracted with EtOAc. The organic layer was dried over MgSO4 and concentrated in vacuo. The resulting yellow gum was purified by reverse phase HPLC (Column: Waters XBridge C18 19×100, 5 μm; Mobile phase A: 0.03% NH4OH in water (v/v); Mobile phase B: 0.03% NH4OH in MeCN (v/v); 95.0% H2O/5.0% MeCN linear to 60% H2O/40% MeCN in 8.5 min, 60% H2O/40% MeCN linear to 0% H2O/100% MeCN in 0.5 min, HOLD at 0% H2O/100% MeCN to 10.0 min. Flow: 25 mL/min) to afford the title compound (9.4 mg, 24%).

後処理

  1. extractionextracted with EtOAc
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customThe resulting yellow gum was purified by reverse phase HPLC (Column: Waters XBridge C18 19×100, 5 μm; Mobile phase A: 0.03% NH4OH in water (v/v); Mobile phase B: 0.03% NH4OH in MeCN (v/v); 95.0% H2O/5.0% MeCN linear to 60% H2O/40% MeCN in 8.5 min, 60% H2O/40% MeCN linear to 0% H2O/100% MeCN in 0.5 min, HOLD at 0% H2O/100% MeCN to 10.0 min. Flow: 25 mL/min)

出典と根拠

ORDレコード
ord-5392d08daf004cdb8d34a43ca3ffc6e9
出典データセット
uspto-grants-2016_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09394285B2

反応ノート

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