Hydrochloric Acid → Dimethyl 4-fluoro-2-nitrophenylmalonate
Reaction equation
[H-].[Na+].[C:3]([O:10][CH3:11])(=[O:9])[CH2:4][C:5]([O:7][CH3:8])=[O:6].F[C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=1[N+:20]([O-:22])=[O:21].Cl>CS(C)=O.CCOC(C)=O>[CH3:8][O:7][C:5](=[O:6])[CH:4]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=1[N+:20]([O-:22])=[O:21])[C:3]([O:10][CH3:11])=[O:9]Participants
Conditions
- Temperature
- 100 °C
Procedure
To a mixture of NaH (60%, 7 g, 0.16 mol) in dimethyl sulfoxide (150 mL) was added dropwise dimethyl malonate (20 mL, 0.16 mol). The mixture was heated to 100° C. for 10 min then cooled to room temperature, followed by the addition of 2,5-difluoronitrobenzene (14 g, 0.08 mol). After stirred at 90° C. for 2 h, the mixture was cooled and poured into 5% aq.HCl with ice cooling. EtOAc (50 mL) was added and the organic phase was separated, washed by water and dried with Na2SO4. The solvent was removed in vacuo to give 2-(4-fluoro-2-nitro-phenyl)-malonic acid dimethyl ester (19.4 g). 2-(4-fluoro-2-nitro-phenyl)-malonic acid dimethyl ester (6 g, 22 mmol) was dissolved in glacial acetic acid (30 mL), the aqueous HCl (6N, 30 mL) was added and the reaction mixture were heated ar refluxing for 4 h, Iron power (5 g, 88 mmol) was added portionwise to the mixture and the refluxing was allowed to continue for another 2 h. The solvent was removed in vacuo and the remaining residue was extracted by EtOAc. The organic phase washed with aqueous HCl (1N), brine and dried over Na2SO4. concentrated to give the titled compound as a yellow solid (3 g, 89%).
Workup
- temperaturethen cooled to room temperature
- temperaturethe mixture was cooled
- additionpoured into 5% aq
- customthe organic phase was separated
- washwashed by water
- dry with materialdried with Na2SO4
- customThe solvent was removed in vacuo
Sources & evidence
- ORD record
- ord-797a2eb75f7e457aad8ed2e595a8a52d
- Source dataset
- uspto-grants-2009_02
- Patent number
- US07495007B2
Reaction notes
Loading…