Sodium Iodide → 3-(4-Methoxypyridin-2-yl)-2,2-dimethyl-propionic acid methyl ester

HRID 2054444Notes

Reaction equation

HRID 2054444 reaction equation
[CH3:1][O:2][C:3](=[O:17])[C:4]([CH3:16])([CH3:15])[CH:5](O)[C:6]1[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[CH:8][N:7]=1.CCN(C(C)C)C(C)C.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[I-].[Na+]>CN(C)C1C=CN=CC=1.ClCCl.[Zn]>[CH3:1][O:2][C:3](=[O:17])[C:4]([CH3:15])([CH3:16])[CH2:5][C:6]1[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[CH:8][N:7]=1

Participants

8

Reactant 4

HCID 5238Sodium IodideHCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 69135147HCID 69135147, compound2×

Product 1

HCID 691343653-(4-Methoxypyridin-2-yl)-2,2-dimethyl-propionic acid methyl esterYield 57.2%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 23994ZincCatalystHCID 6344DichloromethaneSolvent

Procedure

3.0 g of 3-hydroxy-3-(4-methoxypyridin-2-yl)-2,2-dimethyl-propionic acid methyl ester (compound C3), 0.153 g of 4-dimethylaminopyridine and 2.58 ml of N,N′-diisopropylethylamine are dissolved in 80 ml of dichloromethane. Trifluoromethanesulfonic acid anhydride is added dropwise under ice-cooling. The cooling bath is removed and the mixture is stirred at room temperature for 2.5 h. After evaporation in vacuo, the remaining residue is dissolved as obtained in 100 ml of 1,2-dimethoxyethane. 9.37 g of sodium iodide and 16.3 g of activated zinc are added and the mixture is stirred at 100° C. for 1.5 h. The solids are filtered off, the filtrate is diluted with 800 ml of dichloromethane and extracted several times with halfsaturated aqueous sodium chloride solution. The organic layer is dried using sodium sulfate and concentrated. The residue is purified by chromatography on silica gel (toluene/ethyl acetate 2:1) to afford 1.6 g of the title compound as an oil. MS: 224.2 (MH+). TLC: Rf=0.26 (toluene/acetone 2:1).

Workup

  1. temperaturecooling
  2. customThe cooling bath is removed
  3. customAfter evaporation in vacuo
  4. dissolutionthe remaining residue is dissolved
  5. customas obtained in 100 ml of 1,2-dimethoxyethane
  6. stirringthe mixture is stirred at 100° C. for 1.5 h
  7. filtrationThe solids are filtered off
  8. additionthe filtrate is diluted with 800 ml of dichloromethane
  9. extractionextracted several times with halfsaturated aqueous sodium chloride solution
  10. customThe organic layer is dried
  11. concentrationconcentrated
  12. customThe residue is purified by chromatography on silica gel (toluene/ethyl acetate 2:1)

Sources & evidence

ORD record
ord-2a071723637840308096438979570430
Source dataset
uspto-grants-2008_02
Patent number
US07329677B2

Reaction notes

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