Ammonium Chloride → Ethyl 2-(2-Bromo-5-nitro-4-pyridyl)acetate

Temperature

-78 °C

2-Bromo-5-nitropyridine (1.84 g, 9.06 mmol) and trimethylsilanyl-acetic acid ethyl ester (1.53 g, 9.52 mmol) are dissolved under an atmosphere of argon in dry THF (10 ml). After cooling to −78° C., a solution of tetrabutylammonium fluoride (TBAF, 2.37 g, vacuum-dried overnight) in a mixture of THF and acetonitrile (10 ml/10 ml) is slowly added, so that the reaction temperature did not rise above −65° C. After complete addition, the mixture is stirred at −40° C. for 30 minutes, and at −20° C. for 10 minutes. The reaction mixture is re-cooled to −78° C., and 2,3-dichloro-5,6-dicyano-p-benzochinone (DDQ, 2.06 g, 9.06 mmol) is added. The suspension is allowed to warm to RT. TLC analysis indicated complete conversion. The reaction mixture is diluted with EtOAc and poured into a saturated solution of NH4Cl solution. The organic layer is separated, washed with brine, dried over Na2SO4, and the solvent is evaporated. The residue is purified by FCC (toluene/EtOAc 100:0 to 97:3) to afford the title compound. 1H NMR (CDCl3, 400 MHz): δ 1.26 (t, J=7 Hz, 3H), 4.01 (s, 2H), 4.19 (q, J=7 Hz, 2H), 7.53 (s, 1H), 9.06 (s, 1H). ES−−MS: 287, 289 [M−H]−.

1. additionis slowly added, so that the reaction temperature
2. customdid not rise above −65° C
3. additionAfter complete addition
4. waitat −20° C. for 10 minutes
5. temperatureThe reaction mixture is re-cooled to −78° C.
6. addition2,3-dichloro-5,6-dicyano-p-benzochinone (DDQ, 2.06 g, 9.06 mmol) is added
7. temperatureto warm to RT
8. customThe organic layer is separated
9. washwashed with brine
10. dry with materialdried over Na2SO4
11. customthe solvent is evaporated
12. customThe residue is purified by FCC (toluene/EtOAc 100:0 to 97:3)

ORD record

ord-314a67e519074fa9ae03642c03a2e7d6

Source dataset

uspto-grants-2010_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07648989B2