Carbon Dioxide → HCID 21099145, compound

HRID 1351732Notes

Reaction equation

HRID 1351732 reaction equation
Br[C:2]1[CH:10]=[CH:9][C:8]([CH3:11])=[C:7]2[C:3]=1[C:4]([CH2:12][CH2:13][O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])=[CH:5][NH:6]2.[Li]C(C)(C)C.[C:27](=[O:29])=[O:28]>C1COCC1.CCOC(C)=O>[C:18]([Si:15]([CH3:17])([CH3:16])[O:14][CH2:13][CH2:12][C:4]1[C:3]2[C:2]([C:27]([OH:29])=[O:28])=[CH:10][CH:9]=[C:8]([CH3:11])[C:7]=2[NH:6][CH:5]=1)([CH3:21])([CH3:20])[CH3:19]

Participants

6

Reactant 3

HCID 280Carbon DioxideHCID 21099164HCID 21099164, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 21099145HCID 21099145, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a suspension of KH (1.85 g of 30 wt % in oil, 13.85 mmol) in THF (100 mL) was added a solution of 4-bromo-3-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-7-methyl-1H-indole (3.40 g, 9.24 mmol) in THF (10 mL) at 0° C. After stirring for 40 minutes, the solution was cooled to −78° C. and tert-BuLi (10.9 mL of 1.7 M in pentane, 18.47 mmol), precooled to −78° C., was added. After stirring for 1 hour at −78° C., the reaction mixture was transferred to the flask containing anhydrous CO2 (dry ice, 100 g) via cannula under N2 atmosphere at −78° C. The suspension was warmed to room temperature very slowly using cold bath. The mixture was diluted with EtOAc (200 mL) and the organic solution was washed with 1 N HCl (2×200 mL), H2O (200 mL) and brine (200 mL). The organic phase was dried (Na2SO4) and concentrated. The residue was purified by flash chromatography (silica, 15% EtOAc in hexanes) to give 0.74 g (41% based on the recovered SM) of title compound as a white solid. 1H NMR (CDCl3): 300 MHz δ 8.26 (bs, 1H), 7.84 (d, J=7.56 Hz, 1H), 7.32 (d, J=2.46 Hz, 1H), 7.12 (d, J=7.56 Hz, 1H), 3.98 (t, J=6.39 Hz, 2H), 3.33 (t, J=6.39 Hz, 2H), 2.63 (s, 3H), 0.89 (s, 9H), −0.08 (s, 6H).

Workup

  1. customprecooled to −78° C.
  2. additionwas added
  3. stirringAfter stirring for 1 hour at −78° C.
  4. temperatureThe suspension was warmed to room temperature
  5. washthe organic solution was washed with 1 N HCl (2×200 mL), H2O (200 mL) and brine (200 mL)
  6. dry with materialThe organic phase was dried (Na2SO4)
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography (silica, 15% EtOAc in hexanes)
  9. customto give 0.74 g (41%

Sources & evidence

ORD record
ord-f41bc9054e2d42bb87c2e231260cd505
Source dataset
uspto-grants-2007_05
Patent number
US07217730B2

Reaction notes

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