Dicyclohexylamine → 1-(2-Methyl-acryloyl)-2,3-dihydro-1H-indole-2-carboxylic acid

HRID 851544Notes

Reaction equation

HRID 851544 reaction equation
C([O:3][C:4]([CH:6]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[N:7]1[C:15](=[O:19])[C:16]([CH3:18])=[CH2:17])=[O:5])C.[OH-].[K+].C1(NC2CCCCC2)CCCCC1.C1(NC2CCCCC2)CCCCC1.CC(=C)C(N1C2C(=CC=CC=2)CC1C(O)=O)=O>O.C(#N)C.CS(C)=O>[CH3:18][C:16](=[CH2:17])[C:15]([N:7]1[C:8]2[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:14][CH:6]1[C:4]([OH:5])=[O:3])=[O:19]

Participants

8

Reactant 4

HCID 7582DicyclohexylamineHCID 14797Potassium HydroxideHCID 127642221-Methacryloylindoline-2-carboxylic acid ethyl esterHCID 127642242,3-dihydro-1-(2-methyl-1-oxo-2-propenyl)-IH-indole-2-carboxylic acid dicyclohexylamine salt

Product 1

HCID 127642231-(2-Methyl-acryloyl)-2,3-dihydro-1H-indole-2-carboxylic acidYield 50%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of 2,3-dihydro-1-(2-methyl-1-oxo-2-propenyl)-IH-indole-2-carboxylic acid ethyl ester (3.9 g., 15.0 mmole), 80% aqueous dimethylsulfoxide (90 ml.) and potassium hydroxide (86% pellets, 1.3 g., 19.9 mmole), was stirred under nitrogen atmosphere for 2 days at room temperature, then evaporated under reduced pressure on a rotary evaporator to give an oily residue. The residue was dissolved in water (any insoluble material was removed by filtration), and the aqueous solution was made acidic by careful addition of dilute hydrochloric acid, whereby an oil separated. The oily product was extracted with ether, and the ether extract was washed with water (3 times), then with saline. The ether solution was dried over anhydrous magnesium sulfate, and evaporated under reduced pressure to give an oily product. The oil was dissolved in dry acetonitrile, and dicyclohexylamine was added dropwise until the pH of the solution reached approximately 8.5. A crystalline precipitate was filtered. The mixture was allowed to stand overnight at room temperature, and the precipitate was collected on a filter, and the filter residue was washed with ether several times to give 3.46 g. of 2,3-dihydro-1-(2-methyl-1-oxo-2-propenyl)-IH-indole-2-carboxylic acid dicyclohexylamine salt (m.p. 185°-190°). Recrystallization from 2-propanol gave 3.1 g. (50.0%) of the title product as the dicyclohexylamine salt (m.p. 193°-195°) [m.p. means melting point in degrees centigrade, uncorrected.]

Workup

  1. customevaporated under reduced pressure on a rotary evaporator
  2. customto give an oily residue
  3. customwas removed by filtration), and the aqueous solution
  4. additionwas made acidic by careful addition of dilute hydrochloric acid, whereby an oil
  5. customseparated
  6. extractionThe oily product was extracted with ether
  7. extractionthe ether extract
  8. washwas washed with water (3 times)
  9. dry with materialThe ether solution was dried over anhydrous magnesium sulfate
  10. customevaporated under reduced pressure
  11. customto give an oily product
  12. filtrationA crystalline precipitate was filtered
  13. waitto stand overnight at room temperature
  14. customthe precipitate was collected on a filter
  15. washthe filter residue was washed with ether several times
  16. customto give 3.46 g
  17. customRecrystallization from 2-propanol
  18. customgave 3.1 g

Sources & evidence

ORD record
ord-33207fe90e4e40edb2770e95f900aabd
Source dataset
uspto-grants-1983_05
Patent number
US04385180

Reaction notes

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