N-bromobutanimide → Ethyl 6-bromo-3-methoxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carboxylate

HRID 880028Notes

Reaction equation

HRID 880028 reaction equation
[CH3:1][O:2][C:3]1[C:4](=[O:15])[N:5]([CH3:14])[CH:6]=[CH:7][C:8]=1[C:9]([O:11][CH2:12][CH3:13])=[O:10].C1C(=O)N([Br:23])C(=O)C1>ClCCCl>[Br:23][C:6]1[N:5]([CH3:14])[C:4](=[O:15])[C:3]([O:2][CH3:1])=[C:8]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:7]=1

Participants

4

Reactant 2

HCID 67184N-bromobutanimideHCID 15122761Ethyl 3-methoxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carboxylate

Product 1

HCID 71744065Ethyl 6-bromo-3-methoxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carboxylateYield 92.2%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of Intermediate 1 (109 mg, 0.516 mmol) in DCE (2.0 mL) was added NBS (110 mg, 0.619 mmol). The reaction mixture was stirred at rt overnight and then was concentrated under reduced pressure. The residue was diluted with EtOAc, washed with water and brine, dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The residue was dissolved in a small amount of DCM and charged to a 12 g silica gel cartridge which was eluted with a 25 min gradient from 0-100% EtOAc/hexane to give Intermediate 18 (138 mg, 0.476 mmol, 69% yield) as a white solid. HPLC/MS (Method D) RT=1.4 min, [M+1]+ 291.9; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.29 (1H, s), 4.42 (2H, q, J=7.28 Hz), 3.99 (3H, s), 3.55 (3H, s), 1.39 (3H, t, J=7.15 Hz).

Workup

  1. concentrationwas concentrated under reduced pressure
  2. additionThe residue was diluted with EtOAc
  3. washwashed with water and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. dissolutionThe residue was dissolved in a small amount of DCM
  8. additioncharged to a 12 g silica gel cartridge which
  9. washwas eluted with a 25 min gradient from 0-100% EtOAc/hexane

Sources & evidence

ORD record
ord-a043b6cfaab341548af7e5c6d8303afe
Source dataset
uspto-grants-2015_03
Patent number
US08993557B2

Reaction notes

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