Carbon Dioxide → {1-(2-trimethylsilanyl-ethoxymethyl)-1H-indol-7-yl}-oxo-acetic acid methyl ester

HRID 2215761Notes

Reaction equation

HRID 2215761 reaction equation
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[CH:8]=[CH:7]2.[Li]C(C)(C)C.C(=O)=O.[C:27](OC)(=[O:32])[C:28]([O:30][CH3:31])=[O:29]>C1COCC1.CCOC(C)=O>[CH3:31][O:30][C:28](=[O:29])[C:27]([C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[CH:8]=[CH:7]2)=[O:32]

Participants

7

Reactant 4

HCID 280Carbon DioxideHCID 11120Dimethyl oxalateHCID 219500727-Bromo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indoleHCID 178418306HCID 178418306, compound

Product 1

HCID 69641843{1-(2-trimethylsilanyl-ethoxymethyl)-1H-indol-7-yl}-oxo-acetic acid methyl esterYield 84.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 7-bromo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indole (3.0 g, 9.19 mmol) in THF (100 mL) was cooled to −78° C. and a 1.7 M solution of tBuLi in pentanes (15 mL, 25.5 mmol) added dropwise over 15 min. After 15 min, the resultant bright yellow suspension was transferred over 15 min via a cannula cooled with dry ice to a solution of dimethyl oxalate (3.61 g, 30.6 mmol) in THF (40 mL) maintained at −78° C. After 15 min, the mixture was allowed to warm to room temperature and stirred 3 h. The cloudy yellow mixture was treated with pH 7.0 buffer, poured into-EtOAc and the EtOAc washed with pH 7.0 buffer (brine was added to clarify the layers), brine, dried (MgSO4) and concentrated to a cloudy oil. Flash chromatography (10% EtOAc/hexanes) afforded the title compound (2.59 g, 84%) as a bright yellow oil. 1H NMR (400 MHz, DMSO-d6) 7.97 (dd, J=8, 1 Hz, 1H), 7.64 (d, J=3 Hz, 1H), 7.57 (dd, J=8, 1 Hz, 1H), 7.24 (dd, J=8, 8 Hz, 1H), 6.68 (d, J=3 Hz, 1H), 5.59 (s, 2H), 3.91 (s, 3H), 3.04 (t, J=8 Hz, 2H), 0.62 (t, J=8 Hz, 2H), −0.17 (s, 9H). 13C NMR (75.5 MHz, DMSO-d6) 185.17, 163.31, 132.59, 131.60, 130.87, 127.19, 126.15, 120.09, 118.95, 102.40, 77.05, 63.92, 52.83, 16.74, −1.69. IR (CHCl3, cm−1) 1740, 1683. HRMS 334.1481 (M++1, calcd for C17H24NO4Si 334.1475).

Workup

  1. waitthe resultant bright yellow suspension was transferred over 15 min via a cannula
  2. waitAfter 15 min
  3. temperatureto warm to room temperature
  4. additionThe cloudy yellow mixture was treated with pH 7.0 buffer
  5. washthe EtOAc washed with pH 7.0 buffer (brine
  6. additionwas added
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated to a cloudy oil

Sources & evidence

ORD record
ord-87f1fc9458d144928b8f72187f6ae3ea
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Reaction notes

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