Dimethyl methylphosphonate → [2-Oxo4-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-butyl]-phosphonic acid dimethyl ester

HRID 1827684Notes

Reaction equation

HRID 1827684 reaction equation
[CH3:1][P:2](=[O:7])([O:5][CH3:6])[O:3][CH3:4].[Li]CCCC.C([O:15][C:16](=O)[CH2:17][CH2:18][C:19]1[CH:28]=[CH:27][C:26]2[CH2:25][CH2:24][CH2:23][NH:22][C:21]=2[N:20]=1)C>C1COCC1>[CH3:4][O:3][P:2]([CH2:1][C:16](=[O:15])[CH2:17][CH2:18][C:19]1[CH:28]=[CH:27][C:26]2[CH2:25][CH2:24][CH2:23][NH:22][C:21]=2[N:20]=1)(=[O:7])[O:5][CH3:6]

Participants

5

Reactant 3

HCID 12958Dimethyl methylphosphonateHCID 23581268Ethyl 3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-YL)propanoateHCID 178418339Butyllithium

Product 1

HCID 22082659[2-Oxo4-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-butyl]-phosphonic acid dimethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of dimethyl methylphosphonate (1.9 mL, 17.08 mmol) in THF (20 mL) at −78° C. was added nBuLi (10.94 mL, 17.5 mmol). After 30 minutes, 4-9 (1 g , 4.27 mmol) in THF (5 mL) was added. After 1 hour, the reaction was quenched with saturated NH4Cl (10 mL) and warmed to ambient temperature. The mixture was diluted with ethyl acetate, washed with sat. NaHCO3, brine, and dried over MgSO4. Following evaporative removal of the solvent, the residue was chromatographed (silica gel, 70/25/5 CHCl3/EtOAc/MeOH) to give 4-10 as a yellow oil.

Workup

  1. waitAfter 1 hour
  2. customthe reaction was quenched with saturated NH4Cl (10 mL)
  3. additionThe mixture was diluted with ethyl acetate
  4. washwashed with sat. NaHCO3, brine
  5. dry with materialdried over MgSO4
  6. customremoval of the solvent
  7. customthe residue was chromatographed (silica gel, 70/25/5 CHCl3/EtOAc/MeOH)

Sources & evidence

ORD record
ord-7bd1db15ce7d4404ac79c47b98112351
Source dataset
uspto-grants-2006_06
Patent number
US07056909B2

Reaction notes

Loading…