Methyl chlorodifluoroacetate → 6-Methoxy-3-nitro-2-(trifluoromethyl)pyridine

HRID 1297286Notes

Reaction equation

HRID 1297286 reaction equation
Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[C:4]([O:11][CH3:12])[N:3]=1.[F-:13].[K+].Cl[C:16]([F:22])([F:21])C(OC)=O.[NH4+].[OH-].[NH4+].[Cl-]>CN(C=O)C>[CH3:12][O:11][C:4]1[N:3]=[C:2]([C:16]([F:22])([F:13])[F:21])[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 73935Methyl chlorodifluoroacetateHCID 522689Potassium FluorideHCID 27950292-Chloro-6-methoxy-3-nitropyridineHCID 21863491Ammonium chloride ammonium hydroxide

Product 1

HCID 282423586-Methoxy-3-nitro-2-(trifluoromethyl)pyridine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Chloro-6-methoxy-3-nitropyridine (5 g) was heated with Cul (6.05 g), KF(anhydrous, 3.0 g), methyl 2-chloro-2,2-difluoroacetate(6.8 ml) in DMF (28 ml) at 130° C. for 8 hrs. After cooling, it was poured into 1:9 mixture of NH4OH/NH4Cl(100 ml), stirred until homogeneous and extracted with Ethyl acetate. The organic layer were combined, washed with brine and dried (MgSO4), The flash column chromatography (SiO2, 1˜3% EtOAc in heptane) yielded 3.90 g (65%). 1H NMR (CDCl3) δ 4.02, 6.96, 8.10; IR (liq.) 2389 (w), 2254 (w), 2196 (w), 2163 (w), 2017 (w), 1605 (s), 1586 (s), 1538 (s), 1482 (s), 1340 (s), 1290 (s), 1261 (s), 1205 (s), 1180 (s), 1155 (s) cm−1 Anal. Calcd for C7H5F3N2O3: C, 37.85; H, 2.27; N, 12.61; F, 25.66. Found: C, 37.68; H, 2.29; N, 12.30.

Workup

  1. temperatureAfter cooling
  2. extractionextracted with Ethyl acetate
  3. washwashed with brine
  4. dry with materialdried (MgSO4)
  5. customThe flash column chromatography (SiO2, 1˜3% EtOAc in heptane) yielded 3.90 g (65%)

Sources & evidence

ORD record
ord-1b7d9a390d2241da95e621f9b5b54104
Source dataset
uspto-grants-2007_07
Patent number
US07250418B2

Reaction notes

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