Ethyl Acrylate → Ethyl (E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylate

HRID 18314Notes

Reaction equation

HRID 18314 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH2:6][CH2:5]2.[C:13]([O:17][CH2:18][CH3:19])(=[O:16])[CH:14]=[CH2:15].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(C(C)C)CC)(C)C>C(#N)CC.CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[O:12]=[C:7]1[NH:8][C:9]2[N:10]=[CH:11][C:2](/[CH:15]=[CH:14]/[C:13]([O:17][CH2:18][CH3:19])=[O:16])=[CH:3][C:4]=2[CH2:5][CH2:6]1

Participants

8

Reactant 4

HCID 8821Ethyl AcrylateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 110963256-Bromo-3,4-dihydro-1,8-naphthyridin-2(1H)-one

Product 1

HCID 66905192Ethyl (E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylateYield 59%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 7854PropionitrileSolvent

Procedure

A solution of 6-bromo-3,4-dihydro-1H-1,8-naphthyridin-2-one (5.0 g, 21.9 mmole), from Preparation 4, ethyl acrylate (3.3 g, 32.9 mmole), Pd(OAc)2 (1.1 g, 0.74 mmole), tri-ortho-tolylphosphine (1.3 g, 4.4 mmole), and diisopropylethylamine (11.4 mL, 65.7 mmole) in propionitrile (200 mL) and DMF (25 mL) was heated at reflux overnight. The dark mixture was filtered through Celite®, and the filtrate was concentrated. Flash chromatography on silica gel (9:1 CHCl3/CH3OH containing 5% NH4OH) gave the title compound (3.0 g, 59%) as a light yellow solid: MS (ES) m/e 233 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight
  3. filtrationThe dark mixture was filtered through Celite®
  4. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-e848bcc541084c97af96ce82d283157e
Source dataset
uspto-grants-2010_06
Patent number
US07741339B2

Reaction notes

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