Sodium Carbonate → 2-Chloro-5-Methoxynicotinonitrile

HRID 1758497Notes

Reaction equation

HRID 1758497 reaction equation
C1(P(=O)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.S(OS(C(F)(F)F)(=O)=O)(C(F)(F)F)(=O)=O.[Cl:36][C:37]1[N:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][C:38]=1[C:39]([NH2:41])=O.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[Cl:36][C:37]1[N:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][C:38]=1[C:39]#[N:41]

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 13097Triphenylphosphine OxideHCID 67749Trifluoromethanesulfonic anhydrideHCID 12852018HCID 12852018, compound

Product 1

HCID 128520192-Chloro-5-MethoxynicotinonitrileYield 91.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Into a flame dried flask under N2 was placed triphenylphosphine oxide (12.0 g, 0.04 mol) and CH2Cl2 (50 mL) and the mixture cooled to 0°-4° C. A solution of triflic anhydride (6.75 ml, 0.04 mol) in CH2Cl2 (80 mL) was added dropwise. After the addition, the solution was stirred for 15 min. and 2-chloro-5-methoxynicotinamide (8.0 g, 0.04 mol) was added portionwise over 15 minutes. The mixture was allowed to warm to room temperature with stirring overnight, poured into saturated Na2CO3 solution and extracted with CHCl3 (2X). After concentration, the residue was chromatographed on silica gel and the product eluted with CHCl3 to yield 6.2 g (86%) of 2-chloro-5-methoxynicotinonitrile 1H NMR (CDCl3) δ 3.9 (3H, s), 7.5 (1H, d, J=3) and 8.3 (1H, d, J=3); (nujol) 2250 cm-1.

Workup

  1. customInto a flame dried flask under N2
  2. temperaturethe mixture cooled to 0°-4° C
  3. additionAfter the addition
  4. stirringwith stirring overnight
  5. extractionextracted with CHCl3 (2X)
  6. concentrationAfter concentration
  7. customthe residue was chromatographed on silica gel
  8. washthe product eluted with CHCl3

Sources & evidence

ORD record
ord-da550a4e0809425c87e37e5d3f8c01fb
Source dataset
uspto-grants-1983_02
Patent number
US04374140

Reaction notes

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