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

HRID 2175749Notes

Reaction equation

HRID 2175749 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].CCN(C(C)C)C(C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>CN(C=O)C.C(#N)CC.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:13][C:6]1([CH3:14])[C:7](=[O:12])[NH:8][C:9]2[N:10]=[CH:11][C:2](/[CH:17]=[CH:16]/[C:15]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[CH:3][C:4]=2[CH2:5]1

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)acrylateYield 78%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 86641869DMF propionitrileSolvent

Conditions

Temperature
125 °C

Procedure

To a stirred solution of 6-bromo-3,3-dimethyl-3,4-dihydro-1,8-naphthyridin-2(1H)-one (Intermediate-7) (1.3 g, 5.10 mmol), tert-butyl acrylate (3.26 g, 25.50 mmol) in DMF/propionitrile (5 mL/20 mL) was added DIPEA (2.7 mL, 15.30 mmol) at 20-35° C. and the mixture was degassed with N2 for 10 minutes. Then Pd(OAc)2 (114 mg, 0.51 mmol), P(o-tolyl)3 (310 mg, 1.02 mmol) were added, again degassed with N2 for another 10 minutes and heated at 125° C. for 16 h. The reaction mixture was cooled to 20-35° C. and filtered through Celite®. The filtrate was rotary evaporated under vacuum to get residue which was purified by column chromatography using a mixture of 80% ethyl acetate/hexane as an eluent to get the desired compound as a pale yellow solid (1.2 g, 78%); 1H NMR (400 MHz, DMSO-d6) δ 10.66 (s, 1H), 8.37 (d, J=2.0 Hz, 1H), 8.02 (d, J=1.0 Hz, 1H), 7.50 (d, J=15.6 Hz, 1H), 6.51 (d, J=16.1 Hz, 1H), 2.78 (s, 2H), 1.48 (s, 9H), 1.07 (s, 6H).

Workup

  1. customthe mixture was degassed with N2 for 10 minutes
  2. customagain degassed with N2 for another 10 minutes
  3. temperatureThe reaction mixture was cooled to 20-35° C.
  4. filtrationfiltered through Celite®
  5. customThe filtrate was rotary evaporated under vacuum
  6. customto get residue which
  7. customwas purified by column chromatography
  8. additiona mixture of 80% ethyl acetate/hexane as an eluent

Sources & evidence

ORD record
ord-01be7004ef994d69846eaa6319cda76e
Source dataset
uspto-grants-2015_06
Patent number
US09062075B2

Reaction notes

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