Dimethyl methylphosphonate → Dimethyl (2-oxo-6-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)hexyl)phosphonate

HRID 1004270Notes

Reaction equation

HRID 1004270 reaction equation
[CH3:1][P:2](=[O:7])([O:5][CH3:6])[O:3][CH3:4].[Li]CCCC.C[O:14][C:15](=O)[CH2:16][CH2:17][CH2:18][CH2:19][C:20]1[CH:29]=[CH:28][C:27]2[CH2:26][CH2:25][CH2:24][NH:23][C:22]=2[N:21]=1>C1COCC1>[CH3:4][O:3][P:2]([CH2:1][C:15](=[O:14])[CH2:16][CH2:17][CH2:18][CH2:19][C:20]1[CH:29]=[CH:28][C:27]2[CH2:26][CH2:25][CH2:24][NH:23][C:22]=2[N:21]=1)(=[O:7])[O:5][CH3:6]

Participants

5

Reactant 3

HCID 12958Dimethyl methylphosphonateHCID 11265157Methyl 5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanoateHCID 178418339Butyllithium

Product 1

HCID 11267803Dimethyl (2-oxo-6-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)hexyl)phosphonate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of dimethyl methylphosphonate (13.20 g, 106.5 mmol) in anhydrous THF (165 mL) was cooled to -78° and treated dropwise with 2.5 M n-BuLi (42.3 mL). After stirring at -78° for 45 min, a solution of ester 1-5 (6.6 g, 26.6 mmol) in THF (35 mL) was added dropwise and the resulting solution stirred for 30 min -78°, quenched with sat. NH4Cl (100 mL), then extracted with ethyl acetate (3×150 mL). The combined organic extracts were dried (MgSO4), filtered, and concentrated to afford a yellow oil. Chromatography on silica gel (5% MeOH/CH2Cl2) afforded 15-1 as a yellow oil.

Workup

  1. stirringthe resulting solution stirred for 30 min -78°
  2. customquenched with sat. NH4Cl (100 mL)
  3. extractionextracted with ethyl acetate (3×150 mL)
  4. dry with materialThe combined organic extracts were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford a yellow oil

Sources & evidence

ORD record
ord-1ebcabd50e7e41fa8066d5baa8c7fd7d
Source dataset
uspto-grants-2000_04
Patent number
US06048861

Reaction notes

Loading…