Carbon Dioxide → (1-Methyl-1H-indol-7-yl)-oxo-acetic acid methyl ester

HRID 2215753Notes

Reaction equation

HRID 2215753 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2Br)[CH:4]=[CH:3]1.[Li]C(C)(C)C.C(=O)=O.[C:20](OC)(=[O:25])[C:21]([O:23][CH3:24])=[O:22]>C1COCC1.CCOC(C)=O>[CH3:24][O:23][C:21](=[O:22])[C:20]([C:9]1[CH:8]=[CH:7][CH:6]=[C:5]2[C:10]=1[N:2]([CH3:1])[CH:3]=[CH:4]2)=[O:25]

Participants

7

Reactant 4

HCID 280Carbon DioxideHCID 11120Dimethyl oxalateHCID 219500697-Bromo-1-methyl-1H-indoleHCID 178418306HCID 178418306, compound

Product 1

HCID 69642215(1-Methyl-1H-indol-7-yl)-oxo-acetic acid methyl esterYield 57%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 1-methyl-7-bromoindole (1.53 g, 7.29 mmol) in THF (50 mL) was cooled to −78° C. and a 1.7 M solution of tBuLi in pentanes (10 mL, 17 mmol) added dropwise over 10 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 (2.13 g., 18.1 mmol) in THF (40 mL) maintained at −78° C. After 15 min, the mixture was allowed to warm to room temperature and stirred 4 h. The cloudy yellow mixture was treated with pH 7.0 buffer, poured into EtOAc and the EtOAc washed with pH 7.0 buffer, saturated aq NaHCO3, brine, dried (MgSO4) and concentrated to a cloudy oil. Flash chromatography (10% EtOAc/hexanes) afforded the title compound (896 mg, 57%) as a bright yellow oil. 1H NMR (400 MHz, DMSO-d6) 7.97 (d, J=8 Hz, 1H), 7.58 (d, J=8 Hz, 1H), 7.48 (d, J=3 Hz, 1H), 7.20 (dd, J=8 Hz, 1H), 6.66 (d, J=3 Hz, 1H), 3.95 (s, 3H), 3.79 (s, 3H). 13C (75.5 MHz, DMSO-d6) 185.80, 164.31, 133.64, 133.02, 131.23, 128.07, 127.04, 118.77, 118.25, 102.15, 53.01, 37.49. IR (CHCl3, cm−1) 1739, 1678. Anal. Calcd for C12H11NO3: C, 66.35; H, 5.10; N, 6.45. Found: C, 66.48; H, 5.23; N, 6.51.

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
  6. dry with materialsaturated aq NaHCO3, brine, dried (MgSO4)
  7. concentrationconcentrated to a cloudy oil

Sources & evidence

ORD record
ord-8784e4aed62b4720afad02132ab80fdf
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Reaction notes

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