Reaktion #558123

Reaktionsgleichung

HCl

benzyl 3-(1-(tert-butoxy)-2-methoxy-2-oxoethyl)-2-methyl-4-(p-tolyl)-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate

intermediate 14

benzyl 3-(1-(tert-butoxy)-2-methoxy-2-oxoethyl)-2-methyl-4-(p-tolyl)-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate

NaOH

→

2-(6-((benzyloxy)carbonyl)-2-methyl-4-(p-tolyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-2-(tert-butoxy)acetic acid

Ausbeute 85.4%

Lösungsmittel

MeOH

water

EtOAc

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeat room temperature
2. 2
   Sonstigeovernight
3. 3
   WaschenThe organic phase was washed with brine
4. 4
   Trocknendried (Na2SO4)
5. 5
   Einengenconcentrated
6. 6
   SonstigeThe residue was purified by preparative HPLC (10% MeOH/90% H2O/0.1% CF3CO2H, Phenomenex-LUNA 21.1×100 mm, C18, 5 μm column)
7. 7
   SonstigeMeOH removed

Vorschrift

A solution of benzyl 3-(1-(tert-butoxy)-2-methoxy-2-oxoethyl)-2-methyl-4-(p-tolyl)-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate (intermediate 14) (25 mg, 0.048 mmol) in MeOH (1.5 mL) with 1N NaOH (0.48 mL) was stirred at 65° C. for 1 h then at room temperature overnight. The mixture was diluted with water and EtOAc, then neutralized with 1N HCl (0.48 mL). The organic phase was washed with brine, dried (Na2SO4) and concentrated. The residue was purified by preparative HPLC (10% MeOH/90% H2O/0.1% CF3CO2H, Phenomenex-LUNA 21.1×100 mm, C18, 5 μm column). The product-containing fractions were combined and MeOH removed and the remaining aqueous solution lyophilized to provide 2-(6-((benzyloxy)carbonyl)-2-methyl-4-(p-tolyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-2-(tert-butoxy)acetic acid (20.6 mg, 81% yield) as a white powder. 1H NMR (400 MHz, CDCl3) δ ppm 7.29-7.59 (m, 8H), 7.05 (br. s., 1H), 5.13 (br. s., 2H), 5.03 (s, 1H), 4.44 (d, J=18.10 Hz, 1H), 4.13 (d, J=18.10 Hz, 1H), 3.22-3.47 (m, 2H), 2.85 (s, 3H), 2.48 (s, 3H), 1.01 (s, 9H). LCMS (M+H) calcd for C30H35N2O5: 503.25. found: 503.1.

Quelle