4-Methoxy-alpha-toluenethiol → HCID 89704803, Verbindung

Temperatur

100 °C

To a solution of methyl 5-bromo-3,4-difluoro-2-((2-fluorophenyl)amino)benzoate (12.85 g, 35.6 mmol) in anhydrous 1,4-dioxane (30 mL) was added N,N-diisopropylethylamine (9.21 g, 71.2 mmol). Then Pd2(dba)3 (1.63 g, 1.78 mmol) followed by Xantphos (2.06 g, 3.56 mmol) and 4-methoxy-α-toluenethiol (5.48 g, 35.6 mmol) was added under nitrogen atmosphere. The mixture was stirred overnight at 100° C. under N2 atmosphere and then allowed to cool to ambient temperature. The reaction was quenched with water (150 mL) and extracted with ethyl acetate (200 mL×3). The combined organic extract was washed with water (200 mL×3) and brine (200 mL) sequentially, dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography on silica gel (petroleum ether/ethyl acetate, 50:1, v/v) to give the desired product (pale yellow solid, 12.64 g, 82% yield). 1H NMR (400 MHz, CDCl3): δ 9.12 (s, 1H), 7.78 (d, 1H), 7.06-7.44 (m, 6H), 6.82-6.88 (m, 2H), 4.03 (s, 2H), 3.90 (s, 3H), 3.80 (s, 3H).

1. additionwas added under nitrogen atmosphere
2. temperatureto cool to ambient temperature
3. customThe reaction was quenched with water (150 mL)
4. extractionextracted with ethyl acetate (200 mL×3)
5. extractionThe combined organic extract
6. washwas washed with water (200 mL×3) and brine (200 mL) sequentially
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customThe crude product was purified by column chromatography on silica gel (petroleum ether/ethyl acetate, 50:1

ORD-Eintrag

ord-3c85d4748abe4007a519c79361a4b85d

Quelldatensatz

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09290468B2