Sodium Hydroxide → 2-(4-Methoxy-2-nitrophenyl)acetic acid

HRID 1914690Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9](C(OCC)=O)[C:10]([O:12]CC)=[O:11])=[C:5]([N+:20]([O-:22])=[O:21])[CH:4]=1.[OH-].[Na+]>CCO>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:12])=[O:11])=[C:5]([N+:20]([O-:22])=[O:21])[CH:4]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A solution of diethyl (4-methoxy-2-nitrophenyl)malonate (1.1 g; 3.53 mmol; 1 eq) in a mixture of EtOH (25 mL) and sodium hydroxide (25 mL; 1 M; 25 mmol; 7.07 eq) is heated for 1 h at 90° C. The solvents are removed under reduced pressure and the orange-yellow powder is suspended in THF (20 mL). After cooling down to 0° C., 5M HCl (20 mL) is added. The reaction mixture is refluxed at 85° C. for 1 h. After cooling down to room temperature, the 2 phases are separated and the organic phase is dried over MgSO4. The aqueous phase is treated twice with EtOAc (50 mL) and the combined organic phases are dried over MgSO4 then concentrated to dryness to afford 850 mg (100%) of the title compound as a brown solid. 1H NMR (DMSO-d6) δ 8.20-8.10 (m, 1H), 7.45 (d, J=3.0 Hz, 1H), 7.05 (d, J=8.0 Hz, 1H), 6.95 (dd, J=8.0, 3.0 Hz, 1H), 3.78 (s, 2H), 3.67 (s, 3H). HPLC (max plot) 89%; Rt 2.54 min. LC/MS: (ES+): 229.0 (M+NH4+).

Workup

customThe solvents are removed under reduced pressure
temperatureAfter cooling down to 0° C.
addition5M HCl (20 mL) is added
temperatureThe reaction mixture is refluxed at 85° C. for 1 h
temperatureAfter cooling down to room temperature
customthe 2 phases are separated
dry with materialthe organic phase is dried over MgSO4
additionThe aqueous phase is treated twice with EtOAc (50 mL)
dry with materialthe combined organic phases are dried over MgSO4
concentrationthen concentrated to dryness

Sources & evidence

ORD record: ord-3ce8120065ed40428688fe654cdc05ec
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08614215B2

Reaction notes

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