Diisopropylamine → HCID 57722998, compound

HRID 1987034Notes

Reaction equation

HRID 1987034 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[C:13]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])(=[O:15])[CH3:14].Br[CH2:22][C:23]1[C:24]([Cl:37])=[N:25][C:26]([Cl:36])=[CH:27][C:28]=1[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[Cl:35]>C1COCC1.[Cl-].[Na+].O.C(OCC)(=O)C.C(O)(=O)C>[Cl:37][C:24]1[C:23]([CH2:22][CH2:14][C:13]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[C:28]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[Cl:35])[CH:27]=[C:26]([Cl:36])[N:25]=1

Participants

9

Reactant 4

HCID 7912DiisopropylamineHCID 10908tert-Butyl acetateHCID 57722989HCID 57722989, compoundHCID 178418339Butyllithium

Product 1

HCID 57722998HCID 57722998, compoundYield 91%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

n-Butyllithium in hexanes (1.6M, 18 ml, 28.8 mmol) was added to di-isopropylamine (4.1 ml, 29.25 mmol) in dry THF (200 ml) at −10° under nitrogen. After 5 min. the solution was cooled to −70° and tert-butyl acetate (3.9 ml, 28.93 mmol) added dropwise. After stirring at −70° for 15 min. under nitrogen, 3-(bromomethyl)-2,6-dichloro-4-(2-chlorophenyl)pyridine (2.44 g, 6.942 mmol) in dry THF (18 ml) was added dropwise over 10 min., and the mixture stirred at −70° for 1 h. Glacial acetic acid (2.3 ml) was added, the temperature allowed to rise to 22° and brine (200 ml) and ethyl acetate (100 ml) added. The phases were separated and the aqueous further extracted with ethyl acetate (150 ml). The extracts were dried (Na2SO4), evaporated in vacuo and the residue purified by flash chromatography over silica eluting with cyclohexane-ethyl acetate (100:0-50:50) to give the title compound as a viscous gum (2.44 g, 91%).

Workup

  1. temperatureAfter 5 min. the solution was cooled to −70°
  2. stirringthe mixture stirred at −70° for 1 h
  3. customto rise to 22°
  4. customThe phases were separated
  5. extractionthe aqueous further extracted with ethyl acetate (150 ml)
  6. dry with materialThe extracts were dried (Na2SO4)
  7. customevaporated in vacuo
  8. customthe residue purified by flash chromatography over silica eluting with cyclohexane-ethyl acetate (100:0-50:50)

Sources & evidence

ORD record
ord-01837af03117470189c77db87251c528
Source dataset
uspto-grants-2009_06
Patent number
US07550480B2

Reaction notes

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