Isovaleryl chloride → HCID 68719603, compound

HRID 1616686Notes

Reaction equation

HRID 1616686 reaction equation
[CH3:1][CH:2]([CH3:18])[CH2:3][C:4](C1C=C2C(=CC=1)NC(C(O)=O)=C2)=[O:5].[CH2:19]([O:21][C:22]([C:24]1[NH:25][C:26]2[C:31]([C:32]=1[Br:33])=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])[CH3:20].[Al+3].[Cl-].[Cl-].[Cl-].C(Cl)(=O)CC(C)C>[N+](C)([O-])=O>[CH2:19]([O:21][C:22]([C:24]1[NH:25][C:26]2[C:31]([C:32]=1[Br:33])=[CH:30][C:29]([C:4](=[O:5])[CH2:3][CH:2]([CH3:18])[CH3:1])=[CH:28][CH:27]=2)=[O:23])[CH3:20]

Participants

6

Reactant 4

HCID 66054Isovaleryl chlorideHCID 4715017Ethyl 3-Bromoindole-2-carboxylateHCID 6451240Aluminum(III) ChlorideHCID 68720944HCID 68720944, compound

Product 1

HCID 68719603HCID 68719603, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 6375NitromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Preparation of 5-(3-Methyl-butyryl)-1H-indole-2-carboxylic acid (Froshauer, S. A.; Goldstein, S. W.; Stirtan, W. G. U.S. Pat. No. 5,981,762): 3-Bromo-1H-indole-2-carboxylic acid ethyl ester (536 mg, 2.0 mmol), prepared as previously described (Elliott, J. D.; Leber, J. D.; Thompson, S. K.; Halbert, S. M. U.S. Pat. No. 5,684,032) was dissolved in nitromethane (10 mL) and cooled to 0° C. AlCl3 was added to the flask. Then a solution of isovaleryl chloride (0.295 mL, 2.4 mmol) in nitromethane (2 mL) was added dropwise to the flask. The mixture was allowed to come to room temperature and stirred for 18 hours. The mixture was then cooled to 0° C. 20 mL ice-water was added and extracted with CH2Cl2 (4×20 mL). The combined organic phase was washed with saturated brine (20 mL), 1N NaHCO3 (20 mL) and saturated brine (2×20 mL), Dried over anhydrous Na2SO4, filtered, and concentrated under vacuum to give yellow solid. It was then purified by flash column chromatography eluted with hexane:ethyl acetate (6:1) to give 3-Bromo-5-(3-methyl-butyryl)-1H-indole-2-carboxylic acid ethyl ester (468 mg, 67%) as light yellow solid.

Workup

  1. customto come to room temperature
  2. temperatureThe mixture was then cooled to 0° C
  3. extractionextracted with CH2Cl2 (4×20 mL)
  4. washThe combined organic phase was washed with saturated brine (20 mL), 1N NaHCO3 (20 mL) and saturated brine (2×20 mL)
  5. dry with materialDried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customto give yellow solid
  9. customIt was then purified by flash column chromatography
  10. washeluted with hexane:ethyl acetate (6:1)

Sources & evidence

ORD record
ord-f6e75c1312c94b50bb0854517bde25d7
Source dataset
uspto-grants-2014_07
Patent number
US08765802B2

Reaction notes

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