Diisopropylamine → HCID 18946695, compound

HRID 1769198Notes

Reaction equation

HRID 1769198 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH2:13]([N:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19]([C:26]([OH:28])=[O:27])=[CH:18]1)[CH2:14][CH2:15][CH3:16].C([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[C:43]#[N:44])=O.[O:45]1CCC[CH2:46]1>C(OCC)(=O)C.O>[CH2:13]([N:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19]([C:26]([OH:28])=[O:27])=[C:18]1[CH:46]([OH:45])[C:35]1[CH:36]=[CH:31][C:32]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=2[C:43]#[N:44])=[CH:33][CH:34]=1)[CH2:14][CH2:15][CH3:16]

Participants

8

Reactant 5

HCID 7912DiisopropylamineHCID 8028Tetrahydrofuran2×HCID 2519652'-formylbiphenyl-2-carbonitrileHCID 103762901-butylindole-3-carboxylic AcidHCID 178418339Butyllithium

Product 1

HCID 18946695HCID 18946695, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-50 °C

Procedure

To a 3 liter 3-neck flask was added 1 liter of dry tetrahydrofuran and 48.4 ml diisopropylamine. The mixture was cooled to -50° C. under argon, and 216 ml of 1.6M of n-butyllithium (in hexane) was added dropwise over 5 minutes. The mixture was then allowed to warm to -10° C., and then recooled to -40° C. A solution of 30 g of 1-butylindole-3-carboxylic acid in 100 ml dry tetrahydrofuran was added dropwise over 5 minutes. The solution was stirred at -40° to -30° C. for 1 hour, and then recooled to -70° C. At once was added 28.61 g of 2-formyl-2'-cyanobiphenyl, and the mixture was stirred at -70° C. under argon for 2 hours. The mixture then was warmed to -20° C. and 500 ml of water was added while stirring. Ethyl acetate was then added to the mixture and the aqueous layer separated, which was extracted three times with ethyl acetate. The ethyl acetate extracts were combined, washed with 1N HCl, and dried (MgSO4). The solvent was removed under reduced pressure, and the resulting material recrystallized from a mixture of ethyl acetate and hexane, to yield 36.4 g of 1-(n-butyl)-2-[1-hydroxy-1-(2"-cyanobiphenyl-4'yl)methyl]indole-3-carboxylic acid.

Workup

  1. temperatureto warm to -10° C.
  2. customrecooled to -40° C
  3. customrecooled to -70° C
  4. stirringthe mixture was stirred at -70° C. under argon for 2 hours
  5. temperatureThe mixture then was warmed to -20° C.
  6. stirringwhile stirring
  7. customthe aqueous layer separated
  8. extractionwhich was extracted three times with ethyl acetate
  9. washwashed with 1N HCl
  10. dry with materialdried (MgSO4)
  11. customThe solvent was removed under reduced pressure
  12. customthe resulting material recrystallized from a mixture of ethyl acetate and hexane

Sources & evidence

ORD record
ord-c2c13f24935642b19e75ba89d5375a35
Source dataset
uspto-grants-1995_01
Patent number
US05380739

Reaction notes

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