tert-Butyl acrylate → (E)-tert-butyl 3-(6,6-dimethyl-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylate

HRID 2097208Notes

Reaction equation

HRID 2097208 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][CH:11]=1)[NH:8][C:7](=[O:12])[C:6]([CH3:14])([CH3:13])[CH2:5]2.[C:15]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])(=[O:18])[CH:16]=[CH2:17].C(N(C(C)C)C(C)C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:20]([O:19][C:15](=[O:18])/[CH:16]=[CH:17]/[C:2]1[CH:11]=[N:10][C:9]2[NH:8][C:7](=[O:12])[C:6]([CH3:14])([CH3:13])[CH2:5][C:4]=2[CH:3]=1)([CH3:23])([CH3:22])[CH3:21]

Participants

7

Reactant 4

HCID 15458tert-Butyl acrylateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 592775616-Bromo-3,3-dimethyl-1,4-dihydro-1,8-naphthyridin-2-one

Product 1

HCID 59277606(E)-tert-butyl 3-(6,6-dimethyl-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A suspension of 6-bromo-3,3-dimethyl-3,4-dihydro-1,8-naphthyridin-2(1H)-one (434 mg, 1.7 mmol), tert-butyl acrylate (1.23 mL, 8.5 mmol) and (i-Pr)2EtN (0.9 mL, 5.1 mmol) in DMF (25 mL) was de-oxygenated with Ar for 30 min. The mixture was treated with Pd(OAc)2 (38 mg, 0.17 mmol) and P(o-tol)3 (103 mg, 0.34 mmol) then heated to 110° C. for 22 h. The hot mixture was filtered through a pad of celite and washed with ethyl acetate (50 mL). The filtrate was diluted with H2O (100 mL) and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with water, then brine, dried over magnesium sulphate, and concentrated in vacuo. The resulting brown solid was then triturated with a diethyl ether followed by filtration to yield the white solid product. Yield 178 mg (35%); 1H NMR (300 MHz, DMSO-d6) δ 10.68 (s, 1H), 8.39 (s, 1H), 8.04 (s, 1H), 7.52 (d, J=16.1 Hz, 1H), 6.52 (d, J=15.8 Hz, 1H), 2.80 (s, 2H), 1.49 (s, 9H), 1.09 (s, 6H); ESI MS m/z 303 [C17H22N2O3+H]+

Workup

  1. filtrationThe hot mixture was filtered through a pad of celite
  2. washwashed with ethyl acetate (50 mL)
  3. additionThe filtrate was diluted with H2O (100 mL)
  4. extractionextracted with ethyl acetate (2×50 mL)
  5. washThe combined organic layers were washed with water
  6. dry with materialbrine, dried over magnesium sulphate
  7. concentrationconcentrated in vacuo
  8. customThe resulting brown solid was then triturated with a diethyl ether
  9. filtrationfollowed by filtration
  10. customto yield the white solid product

Sources & evidence

ORD record
ord-050524fbffb645b9af786a2de2dd33af
Source dataset
uspto-grants-2013_05
Patent number
US08450307B2

Reaction notes

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