Triethylamine → N-(1-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-2,2-dicyanovinyl)glycine ethyl ester

HRID 1819299Notes

Reaction equation

HRID 1819299 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:7])[CH2:5][NH2:6].[CH2:8](N(CC)CC)C.[C:15]([C:17]([C:35]#[N:36])=[C:18]([N:21]1[CH2:26][CH2:25][CH2:24][C@@H:23]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:22]1)SC)#[N:16].C(=O)([O-])O.[Na+]>C(O)C>[CH2:2]([O:3][C:4](=[O:7])[CH2:5][NH:6][C:18]([N:21]1[CH2:26][CH2:25][CH2:24][C@@H:23]([NH:27][C:28]([O:29][C:30]([CH3:31])([CH3:33])[CH3:32])=[O:34])[CH2:22]1)=[C:17]([C:35]#[N:36])[C:15]#[N:16])[CH3:8]

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 122755Glycine methyl ester hydrochlorideHCID 516892Sodium BicarbonateHCID 86631163tert-butyl {(3R)-1-[2,2-dicyano-1-(methylthio)vinyl]-piperidin-3-yl}carbamate

Product 1

HCID 86625681N-(1-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-2,2-dicyanovinyl)glycine ethyl ester

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
25 °C

Procedure

Glycine methyl ester hydrochloride (3.3 g) and triethylamine (3.7 ml) were added to a solution of tert-butyl {(3R)-1-[2,2-dicyano-1-(methylthio)vinyl]-piperidin-3-yl}carbamate (1.3 g) in ethanol (30 ml), and the resulting mixture was heated under reflux. After 4 hours, triethylamine (1.5 ml) was added thereto, followed by heating under reflux for another 7 hours. After the reaction solution was cooled to 25° C., a saturated aqueous sodium hydrogencarbonate solution was added thereto, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (hexane/ethyl acetate=3/1 to 1/1) to obtain the title compound (360 mg) as a white amorphous substance.

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureunder reflux
  3. temperatureby heating
  4. temperatureunder reflux for another 7 hours
  5. extractionfollowed by extraction with chloroform
  6. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customThe resulting residue was purified by a silica gel column chromatography (hexane/ethyl acetate=3/1 to 1/1)

Sources & evidence

ORD record
ord-1da4cb9c3f544492a671e4870506e232
Source dataset
uspto-grants-2009_10
Patent number
US07601728B2

Reaction notes

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