Hydrochloric Acid → HCID 58270711, compound

HRID 222235Notes

Reaction equation

HRID 222235 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.CCCCCC.[C:19]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)(=[O:21])[CH3:20].[N:28]1[CH:33]=[CH:32][CH:31]=[C:30]([O:34][C:35]([N:37]2[CH2:42][CH2:41][CH:40]([C:43](O)=[O:44])[CH2:39][CH2:38]2)=[O:36])[CH:29]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.Cl>C1COCC1.C(OCC)(=O)C.O>[O:21]=[C:19]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH2:20][C:43]([CH:40]1[CH2:41][CH2:42][N:37]([C:35]([O:34][C:30]2[CH:29]=[N:28][CH:33]=[CH:32][CH:31]=2)=[O:36])[CH2:38][CH2:39]1)=[O:44]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 7410AcetophenoneHCID 7912DiisopropylamineHCID 682631,1'-CarbonyldiimidazoleHCID 574218421-[(Pyridin-3-yloxy)carbonyl]piperidine-4-carboxylic acidHCID 178418244HCID 178418244, compound

Product 1

HCID 58270711HCID 58270711, compoundYield 33%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of diisopropylamine (3.23 g) and THF (20 mL) was cooled to 0° C., and 1.57 M n-butyllithium/hexane (20.4 mL) was slowly added thereto, followed by stirring at the same temperature for 1 hour. Then, the mixture was cooled to −70° C., and acetophenone (3.84 g) was added dropwise thereto, followed by stirring at the same temperature for 1 hour (reaction liquid 1). Meanwhile, to a suspension of 1-[(pyridin-3-yloxy)carbonyl]piperidine-4-carboxylic acid (2.0 g) in THF (30 mL) was added CDI (1.56 g), followed by stirring at room temperature for 1 hour (reaction liquid 2). The reaction liquid 2 was cooled to −70° C., and the reaction liquid 1 was added dropwise thereto, followed by stirring at the same temperature for 1 hour. Then, the mixture was warmed to 0° C. and then warmed to room temperature. To the reaction liquid was added 0.1 M hydrochloric acid (50 mL), then water and ethyl acetate were added thereto, and the organic phase was separated. The organic phase was washed with water and saturated brine, and then dried over magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform/methanol=100/0 to 90/10) to obtain pyridin-3-yl 4-(3-oxo-3-phenylpropanoyl)piperidine-1-carboxylate (0.93 g).

Workup

  1. temperatureThen, the mixture was cooled to −70° C.
  2. stirringby stirring at the same temperature for 1 hour
  3. stirringby stirring at room temperature for 1 hour
  4. temperaturewas cooled to −70° C.
  5. additionwas added dropwise
  6. stirringby stirring at the same temperature for 1 hour
  7. temperatureThen, the mixture was warmed to 0° C.
  8. temperaturewarmed to room temperature
  9. customTo the reaction liquid
  10. customthe organic phase was separated
  11. washThe organic phase was washed with water and saturated brine
  12. dry with materialdried over magnesium sulfate
  13. customThe solvent was evaporated under reduced pressure
  14. customthe residue was purified by silica gel column chromatography (chloroform/methanol=100/0 to 90/10)

Sources & evidence

ORD record
ord-c2a0126a5e5b463b90713f7088cc2b98
Source dataset
uspto-grants-2012_06
Patent number
US08207199B2

Reaction notes

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