Diisopropylamine → HCID 57983363, compound

HRID 1868912Notes

Reaction equation

HRID 1868912 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[C:13]([C:15]1[C:16]([C:21]([CH3:25])([CH3:24])[C:22]#[N:23])=[N:17][CH:18]=[CH:19][CH:20]=1)#[CH:14].Cl[C:27]([O:29][CH2:30][CH3:31])=[O:28]>C1COCC1.O.CO.CCOC(C)=O.CCCCCC>[C:22]([C:21]([C:16]1[C:15]([C:13]#[C:14][C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:20][CH:19]=[CH:18][N:17]=1)([CH3:25])[CH3:24])#[N:23]

Participants

9

Reactant 4

HCID 7912DiisopropylamineHCID 10928Ethyl chloroformateHCID 57983509HCID 57983509, compoundHCID 178418339Butyllithium

Product 1

HCID 57983363HCID 57983363, compoundYield 74%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 21226206Ethyl acetate hexaneSolvent

Procedure

2.5M n-butyllithium (6.6 mL, 16 mmol) was added to a stirred solution of diisopropylamine (2.4 mL, 17 mmol) in THF (20 mL) at −78° C. The reaction mixture was then allowed to warm to ambient temperature for 5 minutes before being cooled back down to −78° C. 2-(3-Ethynylpyridin-2-yl)-2-methylpropanenitrile (0.93 g, 5.5 mmol) was then added dropwise as a solution in THF (20 mL). After 15 minutes, ethyl chloroformate (1.7 mL, 17 mmol) in 5 mL of THF was added to the reaction. The resulting solution was allowed to warm to ambient temperature, and was then stirred for 15 minutes. TLC (30% EtOAc/hexane) showed complete reaction and a slightly lower spot than the starting material. 3 mL of MeOH was added at 8° C. and then 3 mL of H2O was added. The mixture was extracted with EtOAc, and the combined organic layers were washed with water (3×), saturated NH4Cl (3×) and brine (3×). The organic layer was then dried over MgSO4 and concentrated in vacuo. The crude product was purified by silica flash chromatography (0-75% EtOAc/hexane) to give the title compound as a white crystalline solid (0.98 g, 74%). MS (m/z)=243 (M+H)+. Calculated for C14H14N2O2 242.3.

Workup

  1. temperaturebefore being cooled back down to −78° C
  2. temperatureto warm to ambient temperature
  3. customreaction
  4. extractionThe mixture was extracted with EtOAc
  5. washthe combined organic layers were washed with water (3×), saturated NH4Cl (3×) and brine (3×)
  6. dry with materialThe organic layer was then dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by silica flash chromatography (0-75% EtOAc/hexane)

Sources & evidence

ORD record
ord-7db6c3d802d2479784d429df1a8054b1
Source dataset
uspto-grants-2009_12
Patent number
US07635715B2

Reaction notes

Loading…