Acetic Acid → Dimethyl (2-oxo-3-(3-(trifluoromethyl)phenyl)propyl)-phosphonate
Reaction equation
[CH3:1][P:2](=[O:7])([O:5][CH3:6])[O:3][CH3:4].[Li]CCCC.CON(C)[C:16](=[O:28])[CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=1.CC(O)=O>C1(C)C=CC=CC=1.O>[CH3:4][O:3][P:2]([CH2:1][C:16](=[O:28])[CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:26])([F:25])[F:27])[CH:19]=1)(=[O:7])[O:5][CH3:6]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
To a solution of dimethyl methylphosphonate (9.4 g, 75.8 mmol) in toluene (80 mL) at −78° C. was slowly added n-BuLi (2.5M in hexanes, 28 mL, 70 mmol). The reaction mixture was stirred for 1 h and a solution of N-methoxy-N-methyl-2-(3-trifluoromethyl-phenyl)-acetamide (14.39 g) in toluene (50 mL) was slowly added. The reaction mixture was stirred for 2.5 h and AcOH (40 mL) was added. The reaction mixture was warmed to room temperature and water was added. The organic layer was washed with water followed by brine. The organic solution was dried (MgSO4), filtered and concentrated in vacuo. Medium pressure chromatography (CH2Cl2 to 2% MeOH in CH2Cl2) provided the title compound of Preparation 3 (9.37 g). 1H NMR (CDCl3) δ7.52 (m, 1H), 7.44 (m, 2H), 7.37 (m, 1H), 3.96 (s, 2H), 3.87 (s, 3H), 3.76 (s, 3H), 3.12 (d, 2H).
Workup
- customat −78° C.
- stirringThe reaction mixture was stirred for 2.5 h
- washThe organic layer was washed with water
- dry with materialThe organic solution was dried (MgSO4)
- filtrationfiltered
- concentrationconcentrated in vacuo
- customMedium pressure chromatography (CH2Cl2 to 2% MeOH in CH2Cl2) provided
Sources & evidence
- ORD record
- ord-af3e8938c41841b28e0011f348e16a25
- Source dataset
- uspto-grants-2003_11
- Patent number
- US06642266B2
Reaction notes
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