Potassium Carbonate → Tert-butyl 2-cyano-2-(5-nitro-3-(trifluoromethyl)pyridin-2-yl)acetate

HRID 1049999Notes

Reaction equation

HRID 1049999 reaction equation
[C:1]([CH2:3][C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5])#[N:2].C([O-])([O-])=O.[K+].[K+].Cl[C:18]1[C:23]([C:24]([F:27])([F:26])[F:25])=[CH:22][C:21]([N+:28]([O-:30])=[O:29])=[CH:20][N:19]=1>C1COCC1>[C:1]([CH:3]([C:18]1[C:23]([C:24]([F:26])([F:27])[F:25])=[CH:22][C:21]([N+:28]([O-:30])=[O:29])=[CH:20][N:19]=1)[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5])#[N:2]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 70693tert-Butyl cyanoacetateHCID 38491402-Chloro-5-nitro-3-(trifluoromethyl)pyridine

Product 1

HCID 90416649Tert-butyl 2-cyano-2-(5-nitro-3-(trifluoromethyl)pyridin-2-yl)acetateYield 98%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl 2-cyanoacetate (523 mg, 3.71 mmol) in THF (15 mL) was added K2CO3 (854 mg, 6.18 mmol). Then 2-chloro-5-nitro-3-(trifluoromethyl)pyridine (700 mg, 3.09 mmol) was added into the mixture and the mixture was at 50° C. for 10 h. Then the solution was concentrated and distributed between EA and saturated NaHCO3 solution. The combined organic extract was washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by preparative TLC (DCM/MeOH=20:1, Rf=0.4) to yield a light yellow solid of tert-butyl 2-cyano-2-(5-nitro-3-(trifluoromethyl)pyridin-2-yl)acetate (1 g, 3.02 mmol, 98.0% yield): 1H NMR (400 MHz, CD3OD) δ 8.99 (d, J=2.43 Hz, 1H), 8.36 (d, J=2.43 Hz, 1H), 3.35 (s, 1H), 1.49 (d, J=1.54 Hz, 9H); ES-LCMS m/z 276 (M−55).

Workup

  1. concentrationThen the solution was concentrated
  2. extractionThe combined organic extract
  3. washwas washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by preparative TLC (DCM/MeOH=20:1, Rf=0.4)

Sources & evidence

ORD record
ord-28d6da2cd49343eaa53d720b6e8f25af
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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