2,3-Dichloro-5,6-dicyano-1,4-benzoquinone → (5-Bromo-2-nitro-pyridin-3-yl)-acetic acid methyl ester

Temperature

-40 °C

To a suspension of 5-Bromo-2-nitro-pyridine (2.33 g, 11.5 mmol) and trimethylsilanyl-acetic acid methyl ester (1.8 g, 12.0 mmol) in THF (12 mL) is added at −78° C. a solution of dried TBAF (3.0 g, 11.5 mmol), obtained by drying TBAF×3 H2O (7.5 g) for 18 h at 70° C. under high vacuum, in a mixture of acetonitrile (6 mL) and THF (6 mL). The resulting deep red solution is stirred for 1 h at −40° C. TLC analysis indicated complete consumption of starting material. The reaction mixture is cooled to −78° C. and DDQ (2.6 g, 11.5 mmol) is carefully added. The black solution is slowly warmed to RT. Since TLC analysis indicated that no further changes occurred, the reaction mixture is partitioned between EtOAc and a saturated aq. NH4Cl solution. The layers are separated and the organic layer is washed with a saturated aqueous NH4Cl solution, brine, dried over Na2SO4 and concentrated at reduced pressure. The crude product is purified by FCC (cyclohexane/EtOAc 9:1 to 8:1) to afford the title compound as yellow needles. 1H NMR (CDCl3, 400 MHz): δ 3.94 (s, 3H), 4.17 (s, 2H), 8.20 (s, 1H), 8.78 (s, 1H).

1. customobtained
2. dry with materialby drying TBAF×3 H2O (7.5 g) for 18 h at 70° C. under high vacuum
3. additionin a mixture of acetonitrile (6 mL) and THF (6 mL)
4. customconsumption of starting material
5. temperatureThe reaction mixture is cooled to −78° C.
6. temperatureThe black solution is slowly warmed to RT
7. customthe reaction mixture is partitioned between EtOAc
8. customThe layers are separated
9. washthe organic layer is washed with a saturated aqueous NH4Cl solution, brine
10. dry with materialdried over Na2SO4
11. concentrationconcentrated at reduced pressure
12. customThe crude product is purified by FCC (cyclohexane/EtOAc 9:1 to 8:1)

ORD record

ord-824e0b9d5ada4bd89f26ba8e033e79c7

Source dataset

uspto-grants-2010_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07648989B2