Nitromethane → Methyl 3-(2-fluoropyridin-3-yl)-4-nitrobutanoate

HRID 1880130Notes

Reaction equation

HRID 1880130 reaction equation
[F:1][C:2]1[C:7](/[CH:8]=[CH:9]/[C:10]([O:12][CH3:13])=[O:11])=[CH:6][CH:5]=[CH:4][N:3]=1.[N+:14]([CH3:17])([O-:16])=[O:15].CN(C)C(N(C)C)=N>CCOC(C)=O.O>[F:1][C:2]1[C:7]([CH:8]([CH2:17][N+:14]([O-:16])=[O:15])[CH2:9][C:10]([O:12][CH3:13])=[O:11])=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 6375NitromethaneHCID 664601,1,3,3-TetramethylguanidineHCID 59327067(E)-methyl 3-(2-fluoropyridin-3-yl)acrylate

Product 1

HCID 59327206Methyl 3-(2-fluoropyridin-3-yl)-4-nitrobutanoateYield 79%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To (E)-methyl 3-(2-fluoropyridin-3-yl)acrylate (0.945 g, 5.22 mmol) was added nitromethane (10.0 mL, 186 mmol) and 1,1,3,3-tetramethylguanidine (0.120 mL, 0.956 mmol). The reaction mixture was stirred at room temperature for 30 min, heated to 50° C. for 1 h, and diluted with EtOAc and water. The aqueous phase was extracted with EtOAc (2×) and the combined organic extracts were washed with brine (1×), dried over MgSO4, filtered, and concentrated. Purification by flash column chromatography on silica gel (20% to 60% EtOAc in hexanes) gave methyl 3-(2-fluoropyridin-3-yl)-4-nitrobutanoate (0.996 g, 4.11 mmol, 79% yield) as a colorless oil. MS (ESI, pos. ion) m/z: 243.1 (M+1).

Workup

  1. temperatureheated to 50° C. for 1 h
  2. extractionThe aqueous phase was extracted with EtOAc (2×)
  3. washthe combined organic extracts were washed with brine (1×)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by flash column chromatography on silica gel (20% to 60% EtOAc in hexanes)

Sources & evidence

ORD record
ord-cbe20a332ebf4bd7b8e1b2ae41386e80
Source dataset
uspto-grants-2012_11
Patent number
US08318718B2

Reaction notes

Loading…