Diethyl Carbonate → tert-butyl 7-(2-ethoxy-2-oxoethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate

HRID 2299189Notes

Reaction equation

HRID 2299189 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[CH3:13][C:14]1[CH:23]=[CH:22][C:21]2[CH2:20][CH2:19][CH2:18][N:17]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C:16]=2[N:15]=1.[CH2:31]([O:33][C:34](=O)[O:35]CC)[CH3:32]>C1COCC1>[C:27]([O:26][C:24]([N:17]1[C:16]2[N:15]=[C:14]([CH2:13][C:34]([O:33][CH2:31][CH3:32])=[O:35])[CH:23]=[CH:22][C:21]=2[CH2:20][CH2:19][CH2:18]1)=[O:25])([CH3:30])([CH3:29])[CH3:28]

Participants

6

Reactant 4

HCID 7766Diethyl CarbonateHCID 7912DiisopropylamineHCID 17750173tert-Butyl 7-methyl-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylateHCID 178418339Butyllithium

Product 1

HCID 20792300tert-butyl 7-(2-ethoxy-2-oxoethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylateYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of diisopropylamine (7.24 mL, 55.3 mmole) in dry TBF (50 mL) was added n-BuLi (2.5 M in hexanes, 22 mL, 55.3 mmole) dropwise at 0° C. After 15 min, this solution was added dropwise to a solution of 2-methyl-8-(tert-butoxycarbonyl)-5,6,7,8-tetrahydro-1,8-naphthyridine (4.9 g, 19.7 mmole) and diethylcarbonate (8.86 mL, 73.0 mmole) in dry THF (50 mL) at −78° C. After 30 min, the mixture was quenched with saturated NH4Cl (100 mL), warmed to RT, and extracted with EtOAc (3×200 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was chromatographed on silica gel (40% EtOAc/hexanes) to give the title compound (5.72 g, 91%) as a light yellow oil: MS (ES) m/e 321 (M+H)+.

Workup

  1. waitAfter 30 min
  2. customthe mixture was quenched with saturated NH4Cl (100 mL)
  3. extractionextracted with EtOAc (3×200 mL)
  4. dry with materialThe combined organic extracts were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was chromatographed on silica gel (40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-af8a90d46abd484080e662079b9bf179
Source dataset
uspto-grants-2002_12
Patent number
US06495560B1

Reaction notes

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