Formaldehyde → 3-(6-hydroxy-1,3-benzodioxol-5-yl)-3-(hydroxymethyl)-7-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one

HRID 1407467ノート

反応式

HRID 1407467 の反応式
[OH:1][C:2]1[C:3]([CH:11]2[C:19]3[C:14](=[C:15]([C:20]([F:23])([F:22])[F:21])[CH:16]=[CH:17][CH:18]=3)[NH:13][C:12]2=[O:24])=[CH:4][C:5]2[O:9][CH2:8][O:7][C:6]=2[CH:10]=1.[CH2:25]=[O:26].[OH-].[Na+]>O1CCCC1.O>[OH:1][C:2]1[C:3]([C:11]2([CH2:25][OH:26])[C:19]3[C:14](=[C:15]([C:20]([F:23])([F:22])[F:21])[CH:16]=[CH:17][CH:18]=3)[NH:13][C:12]2=[O:24])=[CH:4][C:5]2[O:9][CH2:8][O:7][C:6]=2[CH:10]=1

参加物

6

反応物 3

HCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 673588353-(6-hydroxy-1,3-benzodioxol-5-yl)-7-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one

生成物 1

HCID 673564263-(6-hydroxy-1,3-benzodioxol-5-yl)-3-(hydroxymethyl)-7-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one収率 74.3%

試薬・触媒・溶媒 2

HCID 962Water溶媒2 回HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

To a suspension of 3-(6-hydroxy-1,3-benzodioxol-5-yl)-7-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one (5.64 g, 16.7 mmol), para-formaldehyde (1.78 g, 59.4 mmol) in tetrahydrofuran (20.0 mL) and water (50.0 mL) was added the aqueous solution of sodium hydroxide (2.68 g, 66.9 mmol) in water (30.0 mL). The reaction mixture was stirred at 0° C. for 1 h and quenched with 10% hydrochloric acid (50.0 mL). The mixture was extracted with ethyl acetate (3×50.0 mL). The combined organic solution was washed with saturated ammonium chloride (3×50 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was purified by column chromatography to afford 3-(6-hydroxy-1,3-benzodioxol-5-yl)-3-(hydroxymethyl)-7-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one (4.56 g, 73%) as a fluffy solid: 1H NMR (300 MHz, DMSO-d6) δ 10.63 (s, 1H), 9.16 (s, 1H), 7.32 (d, J=7.9 Hz, 1H), 7.08 (d, J=7.2 Hz, 1H), 7.01 (s, 1H), 6.94 (dd, J=7.7, 7.7 Hz, 1H), 6.18 (s, 1H), 5.88 (s, 2H), 5.03 (br, 1H), 3.97 (ABq, J=9.9 Hz, 2H); 13C NMR (75 MHz, DMSO-d6) δ 180.5, 150.3, 146.8, 141.5, 140.0, 136.0, 127.5, 123.8, 121.0, 117.7, 109.7, 108.4, 101.2, 97.9, 60.2, 55.2; MS (ES+) m/z 390.2 (M+1).

後処理

  1. customquenched with 10% hydrochloric acid (50.0 mL)
  2. extractionThe mixture was extracted with ethyl acetate (3×50.0 mL)
  3. washThe combined organic solution was washed with saturated ammonium chloride (3×50 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo to dryness
  7. customThe residue was purified by column chromatography

出典と根拠

ORDレコード
ord-8c7e52f449604552ba2149d4808b5cea
出典データセット
uspto-grants-2014_12
特許番号
US08916580B2

反応ノート

読み込み中…