Benzyl chloroformate → Benzyl 2-methyl-4-oxo-3,4-dihydropyridine-1(2H)-carboxylate

HRID 1292122Notes

Reaction equation

HRID 1292122 reaction equation
C[O:2][C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1.[CH3:9][Mg]Cl.[CH2:12]([O:19][C:20](Cl)=[O:21])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>O1CCCC1>[CH3:9][CH:7]1[CH2:8][C:3](=[O:2])[CH:4]=[CH:5][N:6]1[C:20]([O:19][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:21]

Participants

5

Reactant 3

HCID 10387Benzyl chloroformateHCID 692784-MethoxypyridineHCID 178418332HCID 178418332, compound

Product 1

HCID 11459227Benzyl 2-methyl-4-oxo-3,4-dihydropyridine-1(2H)-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

The methodology of D. L. Comins and J. D. Brown, Tetrahedron Letters, 1986, pp 4549-4552 was used: To a stirred solution of 2.5 g of 4-methoxypyridine in 75 mL of anhydrous tetrahydrofuran cooled to -23° C. under a nitrogen atmosphere was added 8 mL of 3M methylmagnesium chloride in tetrahydrofuran followed by 4 g of benzylchloroformate, keeping the internal temperature below -20° C. After stirring for 4 h at -25°±5° C., the reaction was quenched with 100 mL of 1N HCl and extracted with 5×100 mL portions of ether. The combined extracts were dried over MgSO4 and concentrated under reduced pressure. Further drying under vacuum gave 5.1 g of 2(R,S)-methyl-1-(benzyloxycarbonyl)-2,3-dihydro-4-pyridone as a greenish oil: TLC (25% EtOAc in hexane); 1H NMR (400 MHz, CDCl3) 7.75 (d, 1H), 7.4 (s, 5H), 5.30 (d, 1H), 5.26 (s, 2H), 4.7 (m, 1H), 2.82 (dd, 1H), 2.38 (d, 2H), 1.25 (t, 3H).

Workup

  1. customthe internal temperature below -20° C
  2. customthe reaction was quenched with 100 mL of 1N HCl
  3. extractionextracted with 5×100 mL portions of ether
  4. dry with materialThe combined extracts were dried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customFurther drying under vacuum

Sources & evidence

ORD record
ord-7ec06c8397b7464aa225dbd7744bfde1
Source dataset
uspto-grants-1998_05
Patent number
US05756508

Reaction notes

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