Dimethylformamide → N-(2-Fluoro-4-iodo-phenyl)-malonamic acid ethyl ester
Reaction equation
[F:1][C:2]1[CH:8]=[C:7]([I:9])[CH:6]=[CH:5][C:3]=1[NH2:4].C(N([CH2:15][CH3:16])CC)C.C([CH:19]([C:23](Cl)=[O:24])[C:20](Cl)=[O:21])C.CN(C=[O:30])C>CN(C1C=CN=CC=1)C>[CH2:15]([O:30][C:23](=[O:24])[CH2:19][C:20]([NH:4][C:3]1[CH:5]=[CH:6][C:7]([I:9])=[CH:8][C:2]=1[F:1])=[O:21])[CH3:16]Participants
6
Conditions
- Temperature
- 60 °C
Procedure
To a solution of 2-fluoro-4-iodoaniline (15.1 g, 63.7 mmol), triethylamine (8.9 mL, 63.7 mmol) and DMAP (100 mg, 0.8 mmol) in DMF (45 mL) was added ethyl malonyl chloride (9.8 mL, 76.4 mmol). The reaction mixture was heated at 60° C. for 2 hours then concentrated in vacuo. The resultant residue was dissolved in ethyl acetate (30 mL), washed with water (20 mL) and the aqueous fraction extracted twice with ethyl acetate (2×10 mL). The combined organic fractions were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 20-30% ethyl acetate in cyclohexane) to yield the title compound as a white solid (19.5 g, 87%). LCMS (Method B): RT=3.43 min, M+H+=352.
Workup
- concentrationthen concentrated in vacuo
- dissolutionThe resultant residue was dissolved in ethyl acetate (30 mL)
- washwashed with water (20 mL)
- extractionthe aqueous fraction extracted twice with ethyl acetate (2×10 mL)
- washThe combined organic fractions were washed with brine
- dry with materialdried (MgSO4)
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-b29dd994dac642ed97e61a6e36b6fd05
- Source dataset
- uspto-grants-2013_07
- Patent number
- US08486963B2
Reaction notes
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