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

HRID 2385046노트

반응식

HRID 2385046 반응식
[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

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매2회HCID 8028Tetrahydrofuran용매

반응 조건

온도
0 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-2a296366ff0140d29d06bf7ba1105f61
출처 데이터셋
uspto-grants-2012_09
특허 번호
US08263606B2

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