Diisopropylamine → HCID 67464385, compound

HRID 2202798Notes

Reaction equation

HRID 2202798 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[Cl:13][C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1.[C:20]([O:24][C:25]([N:27]1[CH:32]2[CH2:33][CH2:34][CH:28]1[CH2:29][C:30](=[O:35])[CH2:31]2)=[O:26])([CH3:23])([CH3:22])[CH3:21].[Cl-].[NH4+]>C1COCC1.C(OCC)(=O)C>[C:20]([O:24][C:25]([N:27]1[CH:32]2[CH2:33][CH2:34][CH:28]1[CH2:29][C:30]([C:19]1[CH:18]=[CH:17][N:16]=[CH:15][C:14]=1[Cl:13])([OH:35])[CH2:31]2)=[O:26])([CH3:23])([CH3:21])[CH3:22]

Participants

8

Reactant 5

HCID 7912DiisopropylamineHCID 122873-ChloropyridineHCID 25517Ammonium ChlorideHCID 2794767tert-Butyl 3-oxo-8-azabicyclo(3.2.1)octane-8-carboxylateHCID 178418339Butyllithium

Product 1

HCID 67464385HCID 67464385, compoundYield 11.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

n-Butyl lithium (2.5M, 3.88 mL, 9.7 mmol) was added dropwise to a solution of diisopropylamine (1.43 mL, 10.13 mmol) in THF (20 mL) at −78° C. under nitrogen, warmed to 0° C., stirred for 30 minutes then re-cooled to −78° C. This was then added to a solution of 3-chloropyridine (0.83 mL, 8.81 mmol) in THF (12 mL) and stirred for 1.5 hours. 3-Oxo-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (1.98 g, 8.81 mmol) in THF (12 mL) was added, the reaction mixture warmed to room temperature for 1.5 hours. Saturated aqueous ammonium chloride and ethyl acetate were added, the organics separated, washed with more saturated aqueous ammonium chloride and brine, dried over magnesium sulphate, filtered and the solvent removed by evaporation under vacuum. The residue was purified by flash chromatography on silica eluting with 0-100% ethyl acetate/pentane. The fractions containing the desired product were concentrated under vacuum to give the title compound (0.34 g). 1H NMR (400 MHz, CDCl3): δ 8.48 (s, 1H), 8.47 (d, 1H), 7.69 (d, 1H), 4.38 (m, broad, 2H), 3.05-2.80 (m, broad, 2H), 2.28-2.0 (broad, 5H), 1.6-1.5 (m, broad, 2H), 1.49 (s, 9H).

Workup

  1. temperaturethen re-cooled to −78° C
  2. stirringstirred for 1.5 hours
  3. temperaturethe reaction mixture warmed to room temperature for 1.5 hours
  4. washthe organics separated, washed with more saturated aqueous ammonium chloride and brine
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. customthe solvent removed by evaporation under vacuum
  8. customThe residue was purified by flash chromatography on silica eluting with 0-100% ethyl acetate/pentane
  9. additionThe fractions containing the desired product
  10. concentrationwere concentrated under vacuum

Sources & evidence

ORD record
ord-969dde0e216d450880ac860533eb4db0
Source dataset
uspto-grants-2016_06
Patent number
US09365564B2

Reaction notes

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