Sodium hydride → (+/-) Ethyl 2-ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoate

HRID 1372369Notes

Reaction equation

HRID 1372369 reaction equation
[H-].[Na+].[CH2:3]([C:5]1[NH:6][C:7](=[O:17])[CH:8]=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:10]=1)[CH3:4].[Li+].[Br-].[CH2:20]([O:22][CH:23]([CH2:29][C:30]1[CH:35]=[CH:34][C:33]([O:36][CH2:37][CH2:38]Br)=[CH:32][CH:31]=1)[C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH3:21]>CN(C=O)C.O>[CH2:20]([O:22][CH:23]([CH2:29][C:30]1[CH:31]=[CH:32][C:33]([O:36][CH2:37][CH2:38][N:6]2[C:7](=[O:17])[CH:8]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[N:10]=[C:5]2[CH2:3][CH3:4])=[CH:34][CH:35]=1)[C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH3:21]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 82050Lithium BromideHCID 11002461Ethyl 2-ethoxy-3-[4-(2-bromoethoxy)-phenyl]propanoateHCID 1354734072-Ethyl-6-phenyl-4(3H)-pyrimidinone

Product 1

HCID 22137696(+/-) Ethyl 2-ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoateYield 20,393.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Procedure

To a stirred suspension of NaH (300 mg, 0.0123 mmol, 60%) in dry DMF (20 mL) at 0° C. was added a solution of (±) 2-ethyl-4-phenyl-1,6-dihydropyrimidin-6-one (1.9 g, 0.0095 mmol) in dry DMF (5 mL). The solution was allowed to stir at room temperature for 20 min. after the effervescence cease. LiBr (1.0 g, 0.012 mmol) was added followed by ethyl 2-ethoxy-3-[4-(2-bromoethoxy)phenyl]propanoate (3.2 g, 0.0095 mmol) (disclosed in U.S. patent application Ser. No. 09/012,585), in dry DMF at room temperature. The reaction mixture was immersed in a preheated oil bath at 80° C. and stirred for 18 h and cooled to room temperature, poured into water and extracted with ethyl acetate (3×10 mL). The combined ethyl acetate layers were washed with brine, dried (Na2SO4) and concentrated. The crude compound was chromatographed over silica gel using ethyl acetate:per. ether (3:7) to yield the title compound as a liquid (900 mg, 21%).

Workup

  1. customat room temperature
  2. customThe reaction mixture was immersed in a preheated oil bath at 80° C.
  3. stirringstirred for 18 h
  4. temperaturecooled to room temperature
  5. extractionextracted with ethyl acetate (3×10 mL)
  6. washThe combined ethyl acetate layers were washed with brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. customThe crude compound was chromatographed over silica gel

Sources & evidence

ORD record
ord-dcf3d0160edd405c94fe0d92f3d4f34b
Source dataset
uspto-grants-2007_01
Patent number
US07157581B2

Reaction notes

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