Methyl 2-fluoro-6-nitrobenzoate → Methyl 2-amino-6-fluorobenzoate

Methyl 2-fluoro-6-nitrobenzoate (715 mg, 3.59 mmol) was dissolved in EtOH/HOAc/(10 mL/10 mL), followed by addition of iron powder (602 mg, 10.8 mmol) at room temperature. The resulting mixture was refluxed under N2 for 2 hrs. After cooling down to room temperature, the brown suspension was partitioned between H2O (30 mL) and Et2O (100 mL). After separation, the aqueous solution was extracted with Et2O (50 mL). The combined organic layers were washed with 1N NaOH (3×50 mL), brine (50 mL), dried on MgSO4, and concentrated on rotary vacuum to afford the expected product, methyl 2-amino-6-fluorobenzoate, an colorless oil which became wax-type solid on standing. The crude compound was pure enough to be used in next step without further purification; 1H NMR (400 MHz, CDCl3) δ ppm 3.89 (s, 3 H), 5.67 (s, 2 H), 6.34 (ddd, J=11.58, 8.06, 1.01 Hz, 1 H), 6.41 (d, J=8.31 Hz, 1 H), 7.13 (td, J=8.18, 5.79 Hz, 1 H); Mass spec. 170.06 (MH+), Calc. for C8H8FNO2 169.05.

1. temperatureThe resulting mixture was refluxed under N2 for 2 hrs
2. customthe brown suspension was partitioned between H2O (30 mL) and Et2O (100 mL)
3. customAfter separation
4. extractionthe aqueous solution was extracted with Et2O (50 mL)
5. washThe combined organic layers were washed with 1N NaOH (3×50 mL), brine (50 mL)
6. customdried on MgSO4
7. concentrationconcentrated on rotary vacuum

ORD record

ord-e226eb6255e74df599f41ac8da865a4b

Source dataset

uspto-grants-2008_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07384931B2