Hydrogen Bromide → Ethyl 2-bromo-3-[4-[2-[2-ethyl-4-methyl-6-oxo-1,6-dihydro-1-pyrimidinyl]ethoxy]phenyl]propionate

HRID 842002

Reaction equation

HRID 842002 reaction equation
[CH2:1]([C:3]1[N:4]([CH2:11][CH2:12][O:13][C:14]2[CH:20]=[CH:19][C:17](N)=[CH:16][CH:15]=2)[C:5](=[O:10])[CH:6]=[C:7]([CH3:9])[N:8]=1)[CH3:2].[BrH:21].N([O-])=O.[Na+].[C:26]([O:30][CH2:31][CH3:32])(=[O:29])[CH:27]=[CH2:28]>CC(C)=O.O.[Cu]I>[Br:21][CH:27]([CH2:28][C:17]1[CH:19]=[CH:20][C:14]([O:13][CH2:12][CH2:11][N:4]2[C:5](=[O:10])[CH:6]=[C:7]([CH3:9])[N:8]=[C:3]2[CH2:1][CH3:2])=[CH:15][CH:16]=1)[C:26]([O:30][CH2:31][CH3:32])=[O:29]

Participants

8

Reactant 4

HCID 260Hydrogen BromideHCID 8821Ethyl AcrylateHCID 219601564-[2-[2-Ethyl-4-methyl-6-oxo-1,6-dihydro-1-pyrimidinyl]ethoxy]anilineHCID 23668193Sodium Nitrite

Product 1

HCID 21960196Ethyl 2-bromo-3-[4-[2-[2-ethyl-4-methyl-6-oxo-1,6-dihydro-1-pyrimidinyl]ethoxy]phenyl]propionateYield 55%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 180AcetoneSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 4-[2-[2-ethyl-4-methyl-6-oxo-1,6-dihydro-1-pyrimidinyl]ethoxy]aniline (2.80 g, 10.26 mmol) (obtained from preparation 22) in acetone (10 ml) was added aqueous HBr (47%, 1 ml) and stirred for 10 min. at 0° C. To the above reaction mixture a solution of NaNO2 (850 mg, 12.30 mmol) in water (1.7 ml) was added slowly dropwise at 0° C. and stirring was continued further for 30 min at the same temperature. To this reaction mixture, ethyl acrylate (6.77 ml, 62.0 mmol) was added and allowed to warm to 30° C. Catalytic amount of copper (I) iodide (20 mg) was added in one portion and the reaction mixture was stirred further for 1 h at 30° C. Acetone was removed under reduced pressure and the resultant residue was extracted with EtOAc (3×10 ml). The combined EtOAc layers were washed with dilute NH3 solution, water, followed by brine; dried over anhydrous Na2SO4 and concentrated to afford the crude compound which was purified by flash chromatography using 40% EtOAc/petroleum ether as eluent to yield the tide compound (2.47 g, 55%).

Workup

  1. stirringstirring
  2. waitwas continued further for 30 min at the same temperature
  3. temperatureto warm to 30° C
  4. stirringthe reaction mixture was stirred further for 1 h at 30° C
  5. customAcetone was removed under reduced pressure
  6. extractionthe resultant residue was extracted with EtOAc (3×10 ml)
  7. washThe combined EtOAc layers were washed with dilute NH3 solution, water
  8. dry with materialdried over anhydrous Na2SO4
  9. concentrationconcentrated
  10. customto afford the crude compound which
  11. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-8c190fbed60041feac2b37dd03361904
Source dataset
uspto-grants-2002_04
Patent number
US06372750B2

Linked notes

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