Hydrochloric Acid → methyl 2-(tert-butoxy)-2-(2-methyl-4-(p-tolyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetate 2 HCl

HRID 470929Notes

Reaction equation

HRID 470929 reaction equation
[C:1]([O:5][CH:6]([C:11]1[C:12]([CH3:38])=[N:13][C:14]2[CH2:15][CH2:16][N:17](C(OCC3C=CC=CC=3)=O)[CH2:18][C:19]=2[C:20]=1[C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=1)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:3])[CH3:2].[ClH:39]>C(Cl)Cl.CO.[Pd]>[ClH:39].[ClH:39].[C:1]([O:5][CH:6]([C:11]1[C:12]([CH3:38])=[N:13][C:14]2[CH2:15][CH2:16][NH:17][CH2:18][C:19]=2[C:20]=1[C:21]1[CH:22]=[CH:23][C:24]([CH3:27])=[CH:25][CH:26]=1)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 86692202benzyl 3-(1-(tert-butoxy)-2-methoxy-2-oxoethyl)-2-methyl-4-(p-tolyl)-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate2×

Product 1

HCID 131731138methyl 2-(tert-butoxy)-2-(2-methyl-4-(p-tolyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetate 2 HCl

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To 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 12) (0.100 g, 0.194 mmol) in CH2Cl2 (2 ml) and methanol (2 ml) was added 10% Pd/C (10.30 mg, 9.68 mmol) followed by HCl (0.024 ml, 0.290 mmol). The mixture was shaken under H2 (50 psi) for 3 h. Celite was added and the mixture was filtered over Celite rinsing with MeOH. Concentration gave a residue which was then dissolved in MeOH and re-filtered then concentrated. The residue was triturated with Et2O and the solids were collected by filtration to give methyl 2-(tert-butoxy)-2-(2-methyl-4-(p-tolyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetate 2 HCl as a white solid. 1H NMR (400 MHz, CD3OD) δ ppm 7.44 (t, J=8.44 Hz, 2H), 7.24 (dd, J=6.85, 18.34 Hz, 2H), 5.08 (s, 1H), 4.10-4.26 (m, 1H), 3.70-3.85 (m, 4H), 3.57-3.70 (m, 2H), 3.21-3.31 (m, 2H), 2.66 (s, 3H), 2.47 (s, 3H), 0.99 (s, 9H). LCMS (M+H) calcd for C23H31N2O3: 383.21. found: 383.1.

Workup

  1. additionCelite was added
  2. filtrationthe mixture was filtered over Celite
  3. washrinsing with MeOH
  4. concentrationConcentration
  5. customgave a residue which
  6. filtrationre-filtered
  7. concentrationthen concentrated
  8. customThe residue was triturated with Et2O
  9. filtrationthe solids were collected by filtration

Sources & evidence

ORD record
ord-43e5fa27192e4d44b7610a2a8045bbf7
Source dataset
uspto-grants-2014_01
Patent number
US08629276B2

Reaction notes

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