Diisopropylamine → HCID 86751250, compound

HRID 1378496Notes

Reaction equation

HRID 1378496 reaction equation
[C:1]([N:8]1[CH2:16][CH2:15][CH:11](C(O)=O)[CH2:10][CH2:9]1)([O:3]C(C)(C)C)=O.C(N1C=CN=C1)(N1C=CN=C1)=O.C(NC(C)C)(C)C.C([Li])CCC.[C:41]([C:44]1[CH:45]=[N:46][CH:47]=[CH:48][CH:49]=1)(=[O:43])[CH3:42].[N-]1C=CN=C1>CCCCCC.CCOC(C)=O.C1COCC1>[OH:43][C:41]([C:44]1[CH:45]=[N:46][CH:47]=[CH:48][CH:49]=1)=[CH:42][C:1]([N:8]1[CH2:9][CH2:10][CH2:11][CH2:15][CH2:16]1)=[O:3]

Participants

10

Reactant 6

HCID 7912DiisopropylamineHCID 95893-AcetylpyridineHCID 682631,1'-CarbonyldiimidazoleHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 3386966ImidazolateHCID 178418339Butyllithium

Product 1

HCID 86751250HCID 86751250, compound

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

To an oven dried 50 mL round bottomed flask with a stirring bar, argon inlet and septum was added Boc-isonipecotic acid (2.50 g, 10.90 mmol), 1,1'-carbonyldiimidazole (1.77 g, 10.90 mmol) and dry THF (20 mL). This solution was stirred at 20° C. for 45 min. To a separate, oven dried, 100 mL round bottomed flask with a stirring bar, argon inlet, low temperature thermometer, and septum was added dry THF (30 mL) and distilled diisopropylamine (1.60 mL, 11.45 mmol). This solution was cooled to -78° C. and n-Butyllithium (4.58 mL, of a 2.5M solution in hexane, 11.45 mmol) was added with a syringe. This solution was aged 20 min. then 3-acetylpyridine (1.25 mL, 11.45 mmol) was added dropwise with a syringe. This mixture was stirred for 30 min. at -78° C. then the imidazolide solution was added via a cannula. The mixture was warmed to 20° C. then diluted with EtOAc (350 mL). This solution was washed with 10% aqueous citric acid, saturated aqueous NaHCO3 solution and brine. Drying (MgSO4), filtration and removal of the solvent in vacuo gave an oil. This material was chromatographed on 120 g of silica gel using 3% 2-propanol in CHCl3 as eluant. 1-(1,1-dimethylethoxycarbonyl)-4-(1-(3-hydroxy-1-oxo-3-(3-pyridinyl)-2-propenyl)piperidine was obtained as an oil.

Workup

  1. customTo an oven dried 50 mL round bottomed flask with a stirring bar, argon inlet
  2. customTo a separate, oven dried
  3. addition100 mL round bottomed flask with a stirring bar, argon inlet, low temperature thermometer, and septum was added dry THF (30 mL)
  4. temperatureThis solution was cooled to -78° C.
  5. waitThis solution was aged 20 min.
  6. stirringThis mixture was stirred for 30 min. at -78° C.
  7. temperatureThe mixture was warmed to 20° C.
  8. washThis solution was washed with 10% aqueous citric acid, saturated aqueous NaHCO3 solution and brine
  9. customDrying
  10. filtration(MgSO4), filtration and removal of the solvent in vacuo
  11. customgave an oil
  12. customThis material was chromatographed on 120 g of silica gel using 3% 2-propanol in CHCl3 as eluant

Sources & evidence

ORD record
ord-e557694cc57742cf9fa3e89f08501a0d
Source dataset
uspto-grants-1997_09
Patent number
US05668148

Reaction notes

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