Dimethyl malonate → Dimethyl 2-(2-fluoro-4-nitrophenyl)malonate
Reaction equation
[H-].[Na+].[C:3]([O:10][CH3:11])(=[O:9])[CH2:4][C:5]([O:7][CH3:8])=[O:6].Br[C:13]1[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][C:14]=1[F:22]>CN(C=O)C>[F:22][C:14]1[CH:15]=[C:16]([N+:19]([O-:21])=[O:20])[CH:17]=[CH:18][C:13]=1[CH:4]([C:3]([O:10][CH3:11])=[O:9])[C:5]([O:7][CH3:8])=[O:6]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 70 °C
Procedure
To a suspension of sodium hydride (NaH, 60%, 0.40 g, 10.0 mmol) in dry DMF (10 mL) under ice cooling was added dimethyl malonate (1.04 mL, 9.1 mmol) dropwise followed by a solution of 1-bromo-2-fluoro-4-nitrobenzene (1.00 g, 4.55 mmol) in dry DMF (3 mL) under an argon atmosphere. The resulting mixture was stirred at 70° C. overnight and then allowed to cool to 21° C. The reaction mixture was quenched with saturated NH4Cl and extracted with ethyl acetate (2×50 mL). The organic layer was dried over MgSO4, concentrated and the residue was purified with silica gel column chromatography (hexane:ethyl acetate, 2:1) to give Dimethyl 2-(2-fluoro-4-nitrophenyl)malonate (86) (0.90 g, 73%) as a light yellowish solid: 1H NMR δ 8.07 (dd, 1H, J=8.6, 2.2 Hz), 7.98 (dd, 1H, J=9.3, 2.2 Hz), 7.74 (dd, 1H, J=8.6, 7.1 Hz), 5.08 (s, 1H), 3.81 (s, 6H).
Workup
- temperatureto cool to 21° C
- customThe reaction mixture was quenched with saturated NH4Cl
- extractionextracted with ethyl acetate (2×50 mL)
- dry with materialThe organic layer was dried over MgSO4
- concentrationconcentrated
- customthe residue was purified with silica gel column chromatography (hexane:ethyl acetate, 2:1)
Sources & evidence
- ORD record
- ord-5d661842539146cdaadee0942f61d032
- Source dataset
- uspto-grants-2014_03
- Patent number
- US08680291B2
Reaction notes
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