Dimethyl methylphosphonate → {6-[6-(4-Methoxy-benzylamino)-pyridin-2-yl]-2-oxo-hexyl}-phosphonic acid dimethyl ester
Reaction equation
[CH3:1][P:2](=[O:7])([O:5][CH3:6])[O:3][CH3:4].[Li]CCCC.C([O:17][C:18](=O)[CH2:19][CH2:20][CH2:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([NH:29][CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=2)[N:24]=1)CCC>C1COCC1>[CH3:4][O:3][P:2]([CH2:1][C:18](=[O:17])[CH2:19][CH2:20][CH2:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([NH:29][CH2:30][C:31]2[CH:32]=[CH:33][C:34]([O:37][CH3:38])=[CH:35][CH:36]=2)[N:24]=1)(=[O:7])[O:5][CH3:6]Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
A solution of dimethyl methylphosphonate (2.48 g, 20 mmol) in anhydrous THF (30 mL) was cooled to −78° and treated dropwise with 2.5 M n-BuLi (8.0 mL). After stirring at −78° for 45 min, a solution of ester 6-6 (1.85 g, 5.0 mmol) in THF (10 mL) was added dropwise and the resulting solution stirred for 30 min at −78°, quenched with sat. NH4Cl (25 mL), then extracted with ethyl acetate (3×75 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated to afford a yellow oil. Chromatography on silica gel (5% MeOH/CH2Cl2) afforded 6-7 as a yellow oil in 89% yield.
Workup
- stirringthe resulting solution stirred for 30 min at −78°
- customquenched with sat. NH4Cl (25 mL)
- extractionextracted with ethyl acetate (3×75 mL)
- dry with materialThe combined organic extracts were dried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated
- customto afford a yellow oil
Sources & evidence
- ORD record
- ord-9f7ec0fb27394acf8b58254f34d9cfe4
- Source dataset
- uspto-grants-2004_02
- Patent number
- US06693101B2
Reaction notes
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