tert-Butyl acrylate → HCID 59277577, compound

HRID 1362455Notes

Reaction equation

HRID 1362455 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH:6]=[CH:5]2.[C:13]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])(=[O:16])[CH:14]=[CH2:15].C(N(C(C)C)C(C)C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>CC([O-])=O.CC([O-])=O.[Pd+2].CS(C)=O.CN(C=O)C>[O:12]=[C:7]1[NH:8][C:9]2[N:10]=[CH:11][C:2](/[CH:15]=[CH:14]/[C:13]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[CH:3][C:4]=2[CH:5]=[CH:6]1

Participants

8

Reactant 4

HCID 15458tert-Butyl acrylateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 125201446-Bromo-1,8-naphthyridin-2(1H)-one

Product 1

HCID 59277577HCID 59277577, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalyst2×HCID 679Dimethyl SulfoxideSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A reaction vessel was charged with 6-bromo-1,8-naphthyridin-2(1H)-one (1.5 g, 6.69 mmol), tert-butyl acrylate (4.86 mL, 33.45 mmol), and (i-Pr)2EtN (3.5 mL, 20.07 mmol) followed by DMF (40 mL). The solution was de-oxygenated with argon for 20 min. The mixture was treated with Pd(OAc)2 (150 mg, 0.67 mmol) and P(o-tol)3 (407 mg, 1.34 mmol) then heated to 100° C. for 15 h (overnight). A TLC analysis indicated that only the starting arylhalide is present. At this time the mixture was a yellow suspension. To this mixture was added 20 DMSO (20 mL) and an additional 75 mg of Pd(OAc)2. The mixture was heated at 100° C. for 24 h. After cooling, the dark mixture was filtered through celite and the filter cake was rinsed with EtOAc (100 mL). The filtrate was extracted with EtOAc (2×100 mL). The combined organic fractions were washed with brine (2×100 mL), H2O (100 mL), dried over MgSO4 and filtered through a pad of silica gel. The filtrate was concentrated to about 50 mL then treated with about 150 mL hexanes to form a precipitate. The precipitate was filtered to give the product as a light brown solid. Yield: 700 mg (39%); 1H-NMR (300 MHz, DMSO-d6) δ 12.36 (s, 1H), 8.83 (d, 1H, J=2.3 Hz), 8.53 (d, 1H, J=2.3 Hz), 7.89 (d, 1H, J=9.0 Hz), 7.64 (d, 1H, J=18.0 Hz), 6.65 (d, 1H, J=18.0 Hz), 6.62 (m, 1H), 1.51 (s, 9H); ESI MS m/z 273 [C15H16N2O3+H]+

Workup

  1. temperatureThe mixture was heated at 100° C. for 24 h
  2. temperatureAfter cooling
  3. filtrationthe dark mixture was filtered through celite
  4. washthe filter cake was rinsed with EtOAc (100 mL)
  5. extractionThe filtrate was extracted with EtOAc (2×100 mL)
  6. washThe combined organic fractions were washed with brine (2×100 mL), H2O (100 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered through a pad of silica gel
  9. concentrationThe filtrate was concentrated to about 50 mL
  10. additionthen treated with about 150 mL hexanes
  11. customto form a precipitate
  12. filtrationThe precipitate was filtered

Sources & evidence

ORD record
ord-eef7beafedfc4a40ac99cf1b7a4d3ec3
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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