Isovaleryl chloride → HCID 68719603, compound

HRID 921974Notes

Reaction equation

HRID 921974 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

Synthesis of 5-(3-Methyl-butyryl)-1H-indole-2-carboxylic acid (Froshauer, S. A. et al., U.S. Pat. No. 5,981,762 (1999)): 3-Bromo-1H-indole-2-carboxylic acid ethyl ester (536 mg, 2.0 mmol), is prepared by following the method given by Elliott, J. D. et al., (U.S. Pat. No. 5,684,032 (1997)) is dissolved in nitromethane (10 mL) and cooled to 0° C. AlCl3 is 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 is allowed to come to room temperature and stirred for 18 hours, and then cooled to 0° C. 20 mL ice-water is added and extracted with CH2Cl2 (4×20 mL). The combined organic phase is 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 is 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. 1H NMR (300 MHz, DMSO-d6) 612.60 (brs, 1H); 8.20 (d, J=1.2 Hz, 1H), 7.97 (dd, J=8.7, 1.8 Hz, 1H), 7.57 (d, J=8.7 Hz, 1H), 4.41 (q, J=6.9 Hz, 2H), 2.98 (d, J=6.9 Hz, 2H), 2.20 (m, 1H), 1.39 (t, J=6.9 Hz, 3H), 0.97 (d, J=6.9 Hz, 6H). EIMS m/z 352.0 (M++H).

Workup

  1. customto come to room temperature
  2. temperaturecooled to 0° C
  3. extractionextracted with CH2Cl2 (4×20 mL)
  4. washThe combined organic phase is 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 is then purified by flash column chromatography
  10. washeluted with hexane:ethyl acetate (6:1)

Sources & evidence

ORD record
ord-65f0f14b092141dc8da806092c2c72c8
Source dataset
uspto-grants-2016_03
Patent number
US09278089B2

Reaction notes

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