Methanol → 4-Bromo-3-fluoro-N-methyl-2-nitroaniline

A solution of N-(4-bromo-3-fluoro-2-nitrophenyl)-2,2,2-trifluoroacetamide (3.42 g, 10.3 mmol) and triphenylphosphine (3.79 g, 14.4 mmol) in tetrahydrofuran (31.0 mL) at 0° C. was treated with methanol (1.67 mL, 41.3 mmol) followed by dropwise addition of diisopropyl azodicarboxylate (2.84 mL, 14.4 mmol), and the resultant reaction mixture was stirred at RT for 2 h. The reaction mixture was quenched with water (10 mL), concentrated in vacuo to remove most of the THF. Water (200 mL) was added and the resultant mixture was extracted with ethyl acetate (200 mL). Layers were separated and the organic layer was washed with brine, dried with sodium sulfate, filtered, and concentrated to give the crude product. Purification by flash column chromatography (100% hexanes to 80% dichloromethane/hexanes) gave the desired product (2.46 g, 96%) as an orange solid. LCMS calculated for C7H7BrFN2O2 (M+H)+: m/z=249.0, 251.0. found: 248.9, 250.9.

1. customthe resultant reaction mixture
2. customThe reaction mixture was quenched with water (10 mL)
3. concentrationconcentrated in vacuo
4. customto remove most of the THF
5. additionWater (200 mL) was added
6. extractionthe resultant mixture was extracted with ethyl acetate (200 mL)
7. customLayers were separated
8. washthe organic layer was washed with brine
9. dry with materialdried with sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated
12. customto give the crude product
13. customPurification by flash column chromatography (100% hexanes to 80% dichloromethane/hexanes)

ORD record

ord-8fd73fc95e814137af80fedb5223f2ad

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09399640B2