Acetamidomalonic acid diethyl ester → HCID 59814445, compound

HRID 1908946Notes

Reaction equation

HRID 1908946 reaction equation
[H-].[Na+].[CH3:3][CH2:4][O:5][C:6]([CH:8]([NH:14][C:15]([CH3:17])=[O:16])[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[O:7].[C:18]([N:25]1[C:37]2[CH:36]=[CH:35][C:34]([CH2:38]Br)=[CH:33][C:32]=2[C:31]2[C:26]1=[CH:27][CH:28]=[CH:29][CH:30]=2)([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19]>C1COCC1>[CH2:12]([O:11][C:9](=[O:10])[C:8]([NH:14][C:15](=[O:16])[CH3:17])([CH2:38][C:34]1[CH:35]=[CH:36][C:37]2[N:25]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:26]3[C:31]([C:32]=2[CH:33]=1)=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:6]([O:5][CH2:4][CH3:3])=[O:7])[CH3:13]

Participants

5

Reactant 3

HCID 14041Acetamidomalonic acid diethyl esterHCID 24758Sodium hydrideHCID 59814418HCID 59814418, compound

Product 1

HCID 59814445HCID 59814445, compoundYield 27.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred suspension of sodium hydride (100 mg of a 60% dispersion in oil, 2.5 mmol) in THF (10 mL) at about 0° C. under an atmosphere of argon, was added dropwise a solution of acetamido diethyl malonate (241 mg, 1.1 mmol) in THF (1 mL). The stirred reaction mixture was allowed to warm to room temperature over about 30 minutes, cooled to about 0° C. and a solution of N-Boc 3-bromomethylcarbazole (400 mg, 1.1 mmol) in THF (2 mL) was added. The stirred reaction mixture was heated at about 60° C. for about 6 h. The cooled reaction mixture was quenched with brine (10 mL), and extracted with ethyl acetate (3×20 mL). The combined organic extracts were washed with water (10 mL), dried (MgSO4) and solvent was removed in vacuo. The crude product was purified using column chromatography on silica gel with 1:1 hexane/ethyl acetate as eluant to afford the product (150 mg, 27% yield). ES-MS (M+H)+ 497.3 (calc. 497.2).

Workup

  1. customThe stirred reaction mixture
  2. temperaturecooled to about 0° C.
  3. customThe stirred reaction mixture
  4. temperaturewas heated at about 60° C. for about 6 h
  5. customThe cooled reaction mixture
  6. customwas quenched with brine (10 mL)
  7. extractionextracted with ethyl acetate (3×20 mL)
  8. washThe combined organic extracts were washed with water (10 mL)
  9. dry with materialdried (MgSO4) and solvent
  10. customwas removed in vacuo
  11. customThe crude product was purified

Sources & evidence

ORD record
ord-04f35be241114bffaad6122543f9d4cb
Source dataset
uspto-grants-2013_12
Patent number
US08598312B2

Reaction notes

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