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

HRID 1789911Notes

Reaction equation

HRID 1789911 reaction equation
[Cu]C#N.[C:4]1([Mg]Br)[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH2:12]([O:14][C:15](=[O:37])[C:16](=[CH:22][C:23]1[CH:24]=[N:25][C:26]([NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[CH:27][CH:28]=1)[C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH3:13].[Cl-].[NH4+]>C1COCC1.CCCCCC>[CH2:20]([O:19][C:17](=[O:18])[CH:16]([CH:22]([C:23]1[CH:24]=[N:25][C:26]([NH:29][C:30]([O:32][C:33]([CH3:34])([CH3:36])[CH3:35])=[O:31])=[CH:27][CH:28]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[C:15]([O:14][CH2:12][CH3:13])=[O:37])[CH3:21]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 543379912-(6-Tert-butoxycarbonylaminopyridin-3-ylmethylene)-malonic acid diethyl esterHCID 178418255HCID 178418255, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 544346512-[(6-Tert-butoxycarbonylamino-pyridin-3-yl)-phenyl-methyl]-malonic acid diethyl esterYield 88%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

To a vigorously stirred suspensin of copper(I)cyanide (1.71 g, 19.06 mmol) in dry THF (18 mL) was added a solution of phenylmagnesium bromide (12.7 mL 3 M in ether, 38.11 mmol) at 0° C. under argon. The mixture was allowed to warm to room temperature, giving a dark brown solution. After 150 minutes a solution of 2-(6-tert-butoxycarbonylamino-pyridin-3-ylmethylene)-malonic acid diethyl ester (1.74 g, 4.76 mmol) in dry THF (19 mL) was added at 0° C. The mixture was left stirring for 3 days 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 suspended in hexane. Filtration of the crystals gave 2-[(6-tert-butoxycarbonylamino-pyridin-3-yl)-phenyl-methyl]-malonic acid diethyl ester (1.85 g, 88%).

Workup

  1. customgiving a dark brown solution
  2. waitThe mixture was left
  3. customThe aqueous layer was separated
  4. extractionextracted with ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. customdried
  7. customRemoval of the solvent in vacuo
  8. customgave a residue, which
  9. filtrationFiltration of the crystals

Sources & evidence

ORD record
ord-97224e5d78f145d2ba09e5fb6f159889
Source dataset
uspto-grants-2006_07
Patent number
US07071175B1

Reaction notes

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