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Formaldehyde → methyl 2-{[3-(6-hydroxy-1,3-benzodioxol-5-yl)-3-(hydroxymethyl)-2-oxo-2,3-dihydro-1H-indol-1-yl]methyl}benzoate

HRID 645010
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HRID 645010 반응식
[OH:1][C:2]1[C:3]([CH:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]([CH2:20][C:21]3[CH:30]=[CH:29][CH:28]=[CH:27][C:22]=3[C:23]([O:25][CH3:26])=[O:24])[C:12]2=[O:31])=[CH:4][C:5]2[O:9][CH2:8][O:7][C:6]=2[CH:10]=1.[CH2:32]=[O:33].C([N-]C(C)C)(C)C.[Li+]>C1COCC1>[OH:1][C:2]1[C:3]([C:11]2([CH2:32][OH:33])[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]([CH2:20][C:21]3[CH:30]=[CH:29][CH:28]=[CH:27][C:22]=3[C:23]([O:25][CH3:26])=[O:24])[C:12]2=[O:31])=[CH:4][C:5]2[O:9][CH2:8][O:7][C:6]=2[CH:10]=1
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참가 물질

5

반응물 3

HCID 712FormaldehydeHCID 2724682Lithium diisopropylamideHCID 12004245methyl 2-{[3-(6-hydroxy-1,3-benzodioxol-5-yl)-2-oxo-2,3-dihydro-1H-indol-1-yl]methyl}benzoate

생성물 1

HCID 58872558methyl 2-{[3-(6-hydroxy-1,3-benzodioxol-5-yl)-3-(hydroxymethyl)-2-oxo-2,3-dihydro-1H-indol-1-yl]methyl}benzoate수율 76.5%

시약·촉매·용매 1

HCID 8028
Tetrahydrofuran
용매

실험 절차

A solution of methyl 2-{[3-(6-hydroxy-1,3-benzodioxol-5-yl)-2-oxo-2,3-dihydro-1H-indol-1-yl]methyl}benzoate (17.1 g, 40.0 mmol) and paraformaldehyde (10.3 g, 330 mmol) in THF (500 mL) was degassed by bubbling through argon for 2 hours. To this solution was added lithium diisopropylamide solution (45.1 mL, 2 M solution, 90.0 mmol) slowly at −78° C. The mixture was stirred at ambient temperature overnight and quenched with saturated ammonium chloride solution. The mixtrue was concentrated in vacuo to remove THF followed by the addition of ethyl acetate (500 mL). The organic layer was washed with water, dried over sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was recrystallized from ethyl acetate/hexanes to give the title compound (13.7 g, 75%): 1H NMR (300 MHz, DMSO-d6) δ 9.20 (s, 1H), 7.95 (dd, 1H), 7.53-7.33 (m, 3H), 7.08-6.82 (m, 4H), 6.53 (d, 1H), 6.25 (s, 1H), 5.93-5.86 (m, 2H), 5.31-5.07 (m, 3H), 4.26-4.17 (m, 1H), 4.00-3.92 (m, 1H), 3.88 (s, 3H); MS (ES+) m/z 448.3 (M+1).

후처리

  1. customby bubbling through argon for 2 hours
  2. customquenched with saturated ammonium chloride solution
  3. concentrationThe mixtrue was concentrated in vacuo
  4. customto remove THF
  5. additionfollowed by the addition of ethyl acetate (500 mL)
  6. washThe organic layer was washed with water
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated in vacuo to dryness
  10. customThe residue was recrystallized from ethyl acetate/hexanes

출처 및 근거

ORD 기록
ord-4fc13d50b7af41caa99fc5d0bc656455
출처 데이터셋
uspto-grants-2010_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07700641B2

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