Ethyl Acetate → Tert-butyl 2-cyano-2-(5-nitro-3-(trifluoromethyl)pyridin-2-yl)acetate

HRID 1050127Notes

Reaction equation

Cl[C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][C:5]([N+:12]([O-:14])=[O:13])=[CH:4][N:3]=1.C([O-])([O-])=O.[K+].[K+].[C:21]([CH2:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])#[N:22].CC(=O)OCC>C1COCC1>[C:21]([CH:23]([C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][C:5]([N+:12]([O-:14])=[O:13])=[CH:4][N:3]=1)[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])#[N:22]

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of 2-chloro-5-nitro-3-(trifluoromethyl)pyridine (5 g, 22.07 mmol) and K2CO3 (6.10 g, 44.1 mmol) in THF (150 mL) was added tert-butyl 2-cyanoacetate (3.74 g, 26.5 mmol). The resulting mixture was stirred at 70° C. overnight under N2. After TLC analysis (PE/EA=10/1) showed the starting material was consumed, the solvent was removed in vacuo. The residue was dissolved in EA (100 mL) and washed with H2O (50 mL) and brine (50 mL). The organic layer was dried over Na2SO4, filtered and concentrated to yield a solid of tert-butyl 2-cyano-2-(5-nitro-3-(trifluoromethyl)pyridin-2-yl)acetate (7 g, 21.13 mmol, 96% yield): 1H NMR (400 MHz, CD3OD) δ 9.08 (s, 1H), 8.59 (br. s., 1H), 4.63 (br. s., 1H), 1.55 (s, 9H); ES-LCMS m/z: 332.1 (M+H).

Workup

customwas consumed
customthe solvent was removed in vacuo
dissolutionThe residue was dissolved in EA (100 mL)
washwashed with H2O (50 mL) and brine (50 mL)
dry with materialThe organic layer was dried over Na2SO4
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-e3304b5a4fe646469c7e43dddedc51d5
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382238B2

Reaction notes

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