Ammonium Chloride → 2-[1-(6-Tert-butoxycarbonylamino-pyridin-3-yl)-2-phenyl-ethyl]-malonic acid diethyl ester

HRID 1789916Notes

Reaction equation

HRID 1789916 reaction equation
[Cu]C#N.[CH2:4]([Mg]Br)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH2:13]([O:15][C:16](=[O:38])[C:17](=[CH:23][C:24]1[CH:25]=[N:26][C:27]([NH:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])=[CH:28][CH:29]=1)[C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH3:14].[Cl-].[NH4+]>C1COCC1>[CH2:21]([O:20][C:18](=[O:19])[CH:17]([CH:23]([C:24]1[CH:25]=[N:26][C:27]([NH:30][C:31]([O:33][C:34]([CH3:35])([CH3:37])[CH3:36])=[O:32])=[CH:28][CH:29]=1)[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[C:16]([O:15][CH2:13][CH3:14])=[O:38])[CH3:22]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 543379912-(6-Tert-butoxycarbonylaminopyridin-3-ylmethylene)-malonic acid diethyl esterHCID 178418546HCID 178418546, compoundHCID 178419663HCID 178419663, compound

Product 1

HCID 540328992-[1-(6-Tert-butoxycarbonylamino-pyridin-3-yl)-2-phenyl-ethyl]-malonic acid diethyl esterYield 53%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a vigorously stirred suspensin of copper(I)cyanide (0.66 g, 7.32 mmol) in dry THF (5 mL) was added a solution of benzylmagnesium bromide (5 mL 2.93 M in ether, 14.64 mmol) at 0° C. under argon. The mixture was allowed to warm to room temperature, giving a dark brown solution. After 60 minutes a solution of 2-(6-tert-butoxycarbonylamino-pyridin-3-ylmethylene)-malonic acid diethyl ester (0.67 g, 1.83 mmol) in dry THF (4 mL) was added at 0° C. The mixture was stirred overnight at room temperature then aqueous ammonium chloride was added. The aqueous layer was separated and extracted with ethyl acetate. The combined organic layers were washed with brine and dried. Removal of the solvent in vacuo gave a residue which was purified by flash chromatography (CH2Cl2/ethyl acetate, 1:0→100:15) to give 2-[1-(6-tert-butoxycarbonylamino-pyridin-3-yl)-2-phenyl-ethyl]-malonic acid diethyl ester (0.44 g, 53%).

Workup

  1. customgiving a dark brown solution
  2. customThe aqueous layer was separated
  3. extractionextracted with ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. customdried
  6. customRemoval of the solvent in vacuo
  7. customgave a residue which
  8. customwas purified by flash chromatography (CH2Cl2/ethyl acetate, 1:0→100:15)

Sources & evidence

ORD record
ord-ff12d0482cde4b349653c5c5b90cce46
Source dataset
uspto-grants-2006_07
Patent number
US07071175B1

Reaction notes

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