Acetamidomalonic acid diethyl ester → Diethyl 2-acetylamino-2-(2-methoxy-6-nitrobenzyl)malonate

HRID 31114

Reaction equation

HRID 31114 reaction equation
[Na].[C:2]([NH:5][CH:6]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:7]([O:9][CH2:10][CH3:11])=[O:8])(=[O:4])[CH3:3].[CH3:17][O:18][C:19]1[CH:26]=[CH:25][CH:24]=[C:23]([N+:27]([O-:29])=[O:28])[C:20]=1[CH2:21]Br>C(O)C.O1CCCC1>[C:2]([NH:5][C:6]([CH2:21][C:20]1[C:23]([N+:27]([O-:29])=[O:28])=[CH:24][CH:25]=[CH:26][C:19]=1[O:18][CH3:17])([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:7]([O:9][CH2:10][CH3:11])=[O:8])(=[O:4])[CH3:3]

Participants

6

Reactant 3

HCID 14041Acetamidomalonic acid diethyl esterHCID 186047Benzene, 2-(bromomethyl)-1-methoxy-3-nitro-HCID 5360545Sodium

Product 1

HCID 21974615Diethyl 2-acetylamino-2-(2-methoxy-6-nitrobenzyl)malonateYield 80.8%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Sodium metal (1.15 g) was dissolved in absolute ethanol (500 mL), and to the resulting solution was added diethyl 2-acetylaminomalonate (9.1 g). After 15 min at room temperature, a solution of 2-methoxy-6-nitrobenzyl bromide (J. Med. Chem. 1977, 20, 190-196) (8.6 g) in tetrahydrofuran (25 mL) was added over 2 min. After 16 h stirring at room temperature the mixture was evaporated. The residue was dissolved in a mixture of ethyl acetate and water. The ethyl acetate layer was separated and washed sequentially with water and brine before drying over anhydrous sodium sulfate. Evaporation was followed by silica gel chromatography eluting initially with dichloromethane, followed by ethyl acetate, to obtain diethyl 2-acetylamino-2-(2-methoxy-6-nitrobenzyl)malonate (10.8 g).

Workup

  1. customwas evaporated
  2. dissolutionThe residue was dissolved in a mixture of ethyl acetate and water
  3. customThe ethyl acetate layer was separated
  4. washwashed sequentially with water and brine
  5. dry with materialbefore drying over anhydrous sodium sulfate
  6. customEvaporation
  7. washeluting initially with dichloromethane

Sources & evidence

ORD record
ord-84343011c121420c8fdf0057aeea6d53
Source dataset
uspto-grants-2008_09
Patent number
US07425550B2

Linked notes

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