Hydrochloric Acid → 7-(4-(benzyloxy)butoxy)-3,4-dihydro-1,8-naphthyridin-2(1H)-one

HRID 1750074Notes

Reaction equation

HRID 1750074 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[N:19]=[C:18]([NH:20][C:21](=[O:26])C(C)(C)C)[C:17]([CH2:27][CH2:28]C(OCC)=O)=[CH:16][CH:15]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1>[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[N:19]=[C:18]2[C:17]([CH2:27][CH2:28][C:21](=[O:26])[NH:20]2)=[CH:16][CH:15]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 66631318Ethyl 3-(6-(4-(benzyloxy)butoxy)-2-pivalamidopyridin-3-yl)propanoate

Product 1

HCID 666339287-(4-(benzyloxy)butoxy)-3,4-dihydro-1,8-naphthyridin-2(1H)-oneYield 54%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of intermediate 9 (1.76 g, 3.9 mmol) in 1,4-dioxane (14 mL) was added 3N HCl (7.1 mL) and the mixture was then heated to reflux for 3 h. The mixture was cooled to rt and then anhydrous K2CO3 was slowly added to neutralize the reaction mixture to pH=8, then extracted with EtOAc. The combined organic layers were washed with water, brine, dried over anhydrous Na2SO4 and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel column (elution with PE/EtOAc=4:1-1:1) to give 7-(4-(benzyloxy)butoxy)-3,4-dihydro-1,8-naphthyridin-2(1H)-one (intermediate 10) (671 mg, 54%) as an oil.

Workup

  1. temperaturethe mixture was then heated
  2. temperatureto reflux for 3 h
  3. extractionextracted with EtOAc
  4. washThe combined organic layers were washed with water, brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by flash chromatography on silica gel column (elution with PE/EtOAc=4:1-1:1)

Sources & evidence

ORD record
ord-7cad54a6ab204ed7adb6c215fd30d0dc
Source dataset
uspto-grants-2015_10
Patent number
US09156822B2

Reaction notes

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