Diisopropylamine → HCID 18999057, compound

HRID 2260800Notes

Reaction equation

HRID 2260800 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[Br:13][C:14]1[CH:15]=[CH:16][C:17]([O:20][CH3:21])=[N:18][CH:19]=1.[N+:22]([C:25]1[CH:32]=[CH:31][CH:30]=[CH:29][C:26]=1[CH:27]=[O:28])([O-:24])=[O:23]>O1CCCC1.CCCCCC>[N+:22]([C:25]1[CH:32]=[CH:31][CH:30]=[CH:29][C:26]=1[CH:27]([C:15]1[C:14]([Br:13])=[CH:19][N:18]=[C:17]([O:20][CH3:21])[CH:16]=1)[OH:28])([O-:24])=[O:23]

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 111012-NitrobenzaldehydeHCID 27348955-Bromo-2-methoxypyridineHCID 178418339Butyllithium

Product 1

HCID 18999057HCID 18999057, compoundYield 130.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent4×HCID 8058HexaneSolvent

Procedure

n-Butyllithium (17.5 ml of a 1.6M hexane solution)in anhydrous tetrahydrofuran (20 ml) was added dropwise to a stirred, cooled (-72° C.) solution of diisopropylamine (3.8 ml) in anhydrous tetrahydrofuran (120 ml) under a nitrogen atmosphere. 5-Bromo-2-methoxypyridine (5.09 g, Eur. J. Med. Chem. 1977, 12, 531) in anhydrous tetrahydrofuran (15 ml) was added dropwise followed by a solution of 2-nitrobenzaldehyde (2.96 g) in anhydrous tetrahydrofuran (20 ml) keeping the temperature of the reaction mixture below -70° C. The reaction mixture was stirred for 3 hours at -60° C. to -70° C. then quenched with saturated aqueous ammonium chloride solution. The organic layer was separated, washed with water then dried (magnesium sulphate) and evaporated to dryness. The residue was combined with crude product from another reaction of identical scale then purified by column chromatography on silica using ethyl acetate/petroleum ether (60-80) (1:4) and the solid obtained recrystallised from dichloromethane/petroleum ether (60-80) to afford the title compound (8.69 g). mp 128°-131° C. Rf =0.69 in 20% diethyl ether/dichloromethane on silica plates; 1H NMR (360 MHz, CDCl3) δ 3.93 (3H, s), 6.42 (1H, s), 7.00 (1H, s), 7.31 (1H, dd, J=1 and 7 Hz), 7.49 (1H, ddd, J=1 and 7 Hz), 7.58 (1H, ddd, J=1 and 7 Hz), 8.02 (1H, dd, J=1 and 7 Hz), 8.19 (1H, s); IR (KBr) 3600-2800 cm-1.

Workup

  1. customthe temperature of the reaction mixture below -70° C
  2. customthen quenched with saturated aqueous ammonium chloride solution
  3. customThe organic layer was separated
  4. washwashed with water
  5. dry with materialthen dried (magnesium sulphate)
  6. customevaporated to dryness
  7. customThe residue was combined with crude product from another reaction of identical scale
  8. customthen purified by column chromatography on silica
  9. customthe solid obtained
  10. customrecrystallised from dichloromethane/petroleum ether (60-80)

Sources & evidence

ORD record
ord-b6ad206d7b6145dd81952b3bb90d9be1
Source dataset
uspto-grants-1995_12
Patent number
US05478933

Reaction notes

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