Carbon Dioxide → (1-[(tert-Butyldimethylsilyloxy)prop-1-yl]-1H-indol-4-yl)oxoacetic Acid Methyl Ester

HRID 751499Notes

Reaction equation

HRID 751499 reaction equation
C([Li])(C)(C)C.Br[C:7]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:8]=1[CH:9]=[CH:10][N:11]2[CH2:16][CH2:17][CH2:18][O:19][Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21].[C:27](OC)(=[O:32])[C:28]([O:30][CH3:31])=[O:29].C(=O)=O>O1CCCC1>[CH3:31][O:30][C:28](=[O:29])[C:27]([C:7]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:8]=1[CH:9]=[CH:10][N:11]2[CH2:16][CH2:17][CH2:18][O:19][Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21])=[O:32]

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 11120Dimethyl oxalateHCID 219500764-Bromo-[3-(tert-butyldimethylsilyloxy)propyl]-1H-indoleHCID 178418306HCID 178418306, compound

Product 1

HCID 67337926(1-[(tert-Butyldimethylsilyloxy)prop-1-yl]-1H-indol-4-yl)oxoacetic Acid Methyl EsterYield 75.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Add tert-butyl lithium (88.1 ml, 149.8 mmol, 1.7 M in hexane) to a solution of 4-Bromo-1-[3-(tert-butyldimethyl-silyloxy)propyl]-1H-indole (22.0 g, 59.92 mmol) in anhydrous tetrahydrofuran (100 ml) at −78° C. Stir the reaction at −78° C. for 20 min. Transfer the mixture into a solution of dimethyl oxalate (24.8 g, 209.72 mmol) in tetrahydrofuran (400 ml) at −40° C. via a dry-ice cooled cannula. Upon complete addition, stir the reaction at −78° C. for 15 minutes and slowly warm to room temperature. Quench the reaction with saturated aqueous ammonium chloride and extract into ethyl acetate. Combine the organic layers, dry over magnesium sulfate, and concentrate under reduced pressure. Purification by flash chromatography and eluting with ethyl acetate:hexane gradient (100% hexane to 15% ethyl acetate:hexane over 90 minutes) gives the title compound (16.89 g, 75%), as a light brown oil. ESMS (M++1): 376.2 m/z.

Workup

  1. customthe reaction at −78° C. for 20 min
  2. customat −40° C.
  3. additionUpon complete addition
  4. stirringstir
  5. customthe reaction at −78° C. for 15 minutes
  6. customQuench
  7. customthe reaction with saturated aqueous ammonium chloride
  8. extractionextract into ethyl acetate
  9. dry with materialdry over magnesium sulfate
  10. concentrationconcentrate under reduced pressure
  11. customPurification by flash chromatography
  12. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-ae53b61c9d6b42b5b108e91bad0cc932
Source dataset
uspto-grants-2008_07
Patent number
US07405305B2

Reaction notes

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