Ethyl Acrylate → potassium 7-(benzyloxy)-2-(ethoxycarbonyl)-3H-pyrrolo[1,2-a]indol-1-olate

HRID 1526413Notes

Reaction equation

HRID 1526413 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][C:13]([C:18]([O:20]CC)=O)=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)([O-])C.[K+:28].[C:29]([O:33][CH2:34][CH3:35])(=[O:32])[CH:30]=[CH2:31]>C1COCC1>[CH2:1]([O:8][C:9]1[CH:17]=[CH:16][C:15]2[N:14]3[CH2:31][C:30]([C:29]([O:33][CH2:34][CH3:35])=[O:32])=[C:18]([O-:20])[C:13]3=[CH:12][C:11]=2[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1.[K+:28]

Participants

5

Reactant 3

HCID 8821Ethyl AcrylateHCID 95721Ethyl 5-(phenylmethoxy)-1H-indole-2-carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 67411890potassium 7-(benzyloxy)-2-(ethoxycarbonyl)-3H-pyrrolo[1,2-a]indol-1-olateYield 61%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
34 °C

Procedure

To a 5000 mL, 3-neck round bottom flask equipped with a mechanical stirrer, a temperature probe, a nitrogen inlet, and a heating mantle was added ethyl 5-(benzyloxy)-1H-indole-2-carboxylate (150 g, 508 mmol) followed by anhydrous THF (2000 mL). To the resulting mixture was added potassium t-butoxide (1.0 M in THF, 762 mL, 762 mmol) via an addition funnel over 15 min (temperature increased from 20° C. to 26° C. over the addition time). The mixture was stirred for 1 h and ethyl acrylate (166 mL, 1.52 mol) was added via addition funnel over 15 min (temp increase to 34° C.). The addition funnel was replaced with a reflux condenser and the mixture heated to reflux and stirred for 18 h (the product started to appear as a white precipitate after only 0.5 h of heating). The flask was cooled to room temperature. The resulting precipitate was collected by vacuum filtration. The filtrate was concentrated to approximately 750 mL and diluted with MTBE (approx. 500 mL). Additional product precipitated and this material was filtered and added to the original filter cake. The combined solids were washed with cold THF:MTBE (1:1) and vacuum oven dried (45° C., 2 Ton) to give potassium 7-(benzyloxy)-2-(ethoxycarbonyl)-3H-pyrrolo[1,2-a]indol-1-olate as an off-white solid (120 g, 61% yield). Exact mass calculated for C21H19NO4 (protonated keto-enol form): 349.1, found: LCMS m/z=350.3, [M+H+]; 1H NMR (400 MHz, d6-DMSO) δ ppm 1.18 (t, J=7.1 Hz, 3 H), 3.99 (q, J=7.1 Hz, 2 H), 4.59 (s, 2 H), 5.09 (s, 2 H), 6.14 (s, 1 H), 6.80 (dd, J1=8.8, J2=2.3 Hz, 1 H), 7.11 (d, J=2.3 Hz, 1 H), 7.30 (m, 2 H), 7.38 (m, 2 H), 7.46 (m, 2 H).

Workup

  1. customTo a 5000 mL, 3-neck round bottom flask equipped with a mechanical stirrer
  2. temperatureincreased from 20° C. to 26° C. over the addition time)
  3. customThe addition funnel was replaced with a reflux condenser
  4. temperaturethe mixture heated
  5. temperatureto reflux
  6. stirringstirred for 18 h (the product
  7. waitto appear as a white precipitate after only 0.5 h
  8. temperatureof heating)
  9. temperatureThe flask was cooled to room temperature
  10. filtrationThe resulting precipitate was collected by vacuum filtration
  11. concentrationThe filtrate was concentrated to approximately 750 mL
  12. additiondiluted with MTBE (approx. 500 mL)
  13. customAdditional product precipitated
  14. filtrationthis material was filtered
  15. additionadded to the original filter cake
  16. washThe combined solids were washed with cold THF:MTBE (1:1) and vacuum oven
  17. customdried (45° C., 2 Ton)

Sources & evidence

ORD record
ord-bbcc941a8f4940a9af5f470f2c5675e2
Source dataset
uspto-grants-2015_07
Patent number
US09085581B2

Reaction notes

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