Tetraethoxysilane → Ethyl 2-(7-methoxy-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetate

HRID 707771

반응식

HRID 707771 반응식
I[C:2]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:3]=1[NH2:4].O=[C:12]1[CH2:16][CH2:15][CH2:14][CH:13]1[CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19].[Si](OCC)(OCC)(OCC)OCC.CCN(C(C)C)C(C)C>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC1C=CC(S(O)(=O)=O)=CC=1>[CH3:10][O:9][C:7]1[CH:6]=[CH:5][C:3]2[NH:4][C:12]3[CH:13]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:14][CH2:15][C:16]=3[C:2]=2[CH:8]=1

참가 물질

8

반응물 4

HCID 6517TetraethoxysilaneHCID 81531DiisopropylethylamineHCID 2723663Ethyl 2-(2-oxocyclopentyl)acetateHCID 110103362-Iodo-4-methoxyphenylamine

생성물 1

HCID 67211141Ethyl 2-(7-methoxy-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetate수율 86.6%

시약·촉매·용매 3

HCID 6101p-Toluenesulfonic acid촉매HCID 167845palladium(II) acetate촉매HCID 6228Dimethylformamide용매

반응 조건

온도
135 °C

실험 절차

2-Iodo-4-methoxyaniline (2.0 g, 8.03 mmol) and ethyl 2-(2-oxocyclopentyl)acetate (2.05 g, 12.1 mmol) were dissolved in DMF (30 mL) and tetraethyl orthosilicate (2.12 g, 10.4 mmol) and pyridinum p-toluenesulfonate (PPTS) (0.081 g, 0.321 mmol) were added. The reaction mixture was heated and stirred at 135° C. for 4 h. After cooling to 120° C., DIEA (3.11 g, 24.09 mmol) and palladium (II) acetate (0.054 g, 0.241 mmol) were added. The reaction mixture was stirred for 3 h and then partitioned between ethyl acetate and water. The aqueous layer was extracted twice with ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered and concentrated under reduced pressure. The resultant solution was diluted with 50% ethyl acetate in hexanes and filtered through a pad of silica gel. The filtrate was concentrated and purified by silica gel column chromatography to give 1.9 g of ethyl 2-(7-methoxy-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetate containing residual ethyl 2-(2-oxocyclopentyl)acetate. The mixture was dissolved in DCM (80 mL) and cooled to 0° C. Boron tribromide (21.0 mL, 21.0 mmol, 1.0 M in DCM) was added and the reaction was stirred for 1.5 h. Ice water was added and the reaction mixture was allowed to reach room temperature. The aqueous mixture was extracted three times with DCM. The combined organics were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound (650 mg). LCMS m/z=260.3 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 1.29 (t, J=7.2 Hz, 3H), 2.05-2.14 (m, 1H), 2.50 (dd, J=16.8, 11.2 Hz, 1H), 2.68-2.86 (m, 4H), 3.48-3.58 (m, 1H), 4.16-4.24 (m, 2H), 6.66 (dd, J=8.6, 2.4 Hz, 1H), 6.85 (d, J=2.4 Hz, 1H), 7.15 (d, J=8.7 Hz, 1H), 8.4 (s, 1H).

후처리

  1. temperatureThe reaction mixture was heated
  2. temperatureAfter cooling to 120° C.
  3. stirringThe reaction mixture was stirred for 3 h
  4. custompartitioned between ethyl acetate and water
  5. extractionThe aqueous layer was extracted twice with ethyl acetate
  6. dry with materialThe combined organic extracts were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. additionThe resultant solution was diluted with 50% ethyl acetate in hexanes
  10. filtrationfiltered through a pad of silica gel
  11. concentrationThe filtrate was concentrated
  12. custompurified by silica gel column chromatography

출처 및 근거

ORD 기록
ord-be294918548e4ae293f10f2cfa4d1a0d
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09175320B2

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