Diisopropylamine → HCID 9953666, compound

HRID 1459396Notes

Reaction equation

HRID 1459396 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.C([N-]C(C)C)(C)C.[Li+].C(O[C:24](=[O:40])[CH:25]([CH2:33][C:34]1[CH:39]=[CH:38][N:37]=[CH:36][CH:35]=1)[CH2:26][C:27]1[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=1)C.[C:41]12([NH:51][C:52](=[O:55])[CH2:53]Br)[CH2:50][CH:45]3[CH2:46][CH:47]([CH2:49][CH:43]([CH2:44]3)[CH2:42]1)[CH2:48]2>C1COCC1>[C:41]12([N:51]3[C:52](=[O:55])[CH2:53][C:25]([CH2:26][C:27]4[CH:28]=[CH:29][N:30]=[CH:31][CH:32]=4)([CH2:33][C:34]4[CH:35]=[CH:36][N:37]=[CH:38][CH:39]=4)[C:24]3=[O:40])[CH2:50][CH:45]3[CH2:46][CH:47]([CH2:49][CH:43]([CH2:44]3)[CH2:42]1)[CH2:48]2

Participants

7

Reactant 5

HCID 7912DiisopropylamineHCID 2724682Lithium diisopropylamideHCID 23626599HCID 23626599, compoundHCID 54394614HCID 54394614, compoundHCID 178418339Butyllithium

Product 1

HCID 9953666HCID 9953666, compoundYield 14.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-25 °C

Procedure

To a distilled THF solution (30 ml) at -78° C. under a nitrogen atmosphere containing diisopropylamine (1.13 ml, 8.032 mmol distilled from sodium metal) was added butyllithium (BuLi) (8.032 mmol). The solution was allowed to warm to approximately -25° C., recooled to -78° C. and stirred for 1 hour. The lithium diisopropylamide (LDA) solution was added (via cannula) to a separate flask containing 3-pyridin4-yl-2-pyridin-4-ylmethyl-propionic acid ethyl ester (2.056 g, 8.032 mmol) in THF (30 ml) at -78° C. The red mixture was allowed to warm to approx. -25° C., recooled to -78° C., and stirred for 1 hour. To this lithium enolate solution was added (via cannula) a solution of N-adamantan-1-yl-2-bromo-acetamide (2.186 g, 8.032 mmol) in THF (10 ml) at -78° C. The mixture was kept at -78° C. for 16 hours, warmed to ambient temperature and stirred for two additional hours. The mixture was quenched with EtOAc, washed with an equal volume of H2O and brine, dried (Na2SO4) and concentrated in vacuo to a brown oil. The crude mixture was chromatographed on silica gel (1:1 acetone:hexane) to afford 475 mg (14%) of the title compound as a white solid, which was recrystallized from isopropyl ether, mp 137°-138.5° C.

Workup

  1. customrecooled to -78° C.
  2. temperatureto warm to approx. -25° C.
  3. customrecooled to -78° C.
  4. stirringstirred for 1 hour
  5. waitThe mixture was kept at -78° C. for 16 hours
  6. temperaturewarmed to ambient temperature
  7. stirringstirred for two additional hours
  8. customThe mixture was quenched with EtOAc
  9. washwashed with an equal volume of H2O and brine
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated in vacuo to a brown oil
  12. customThe crude mixture was chromatographed on silica gel (1:1 acetone:hexane)

Sources & evidence

ORD record
ord-1a8fcce18026459e8efde0e2c6d9516a
Source dataset
uspto-grants-1998_12
Patent number
US05854232

Reaction notes

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