Chloromethyl Methyl Ether → 4-(5-Fluoro-2-methoxyphenyl)-2-methoxymethoxy-4-methyl-2-trifluoromethylpentanoic acid ethyl ester
Reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6](=[O:26])[C:7]([OH:25])([C:21]([F:24])([F:23])[F:22])[CH2:8][C:9]([C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[O:19][CH3:20])([CH3:11])[CH3:10])[CH3:4].[CH3:27][O:28][CH2:29]Cl.[Cl-].[NH4+]>CN(C=O)C>[CH2:3]([O:5][C:6](=[O:26])[C:7]([O:25][CH2:27][O:28][CH3:29])([C:21]([F:22])([F:23])[F:24])[CH2:8][C:9]([C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[O:19][CH3:20])([CH3:11])[CH3:10])[CH3:4]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
To a suspension of 525 mg (13.1 mmol) of 60% sodium hydride in mineral oil in 25 mL of dry DMF was added 3.1 g (8.8 mmol) of 4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentanoic acid ethyl ester (see Example 1) in several portions. The mixture was stirred for 15 minutes and was then treated with 1.4 mL (18.4 mmol) of chloromethyl methyl ether in several portions. After 15 minutes, the mixture was poured into 60 mL of saturated aqueous ammonium chloride and extracted with three 25 mL portions of EtOAc. The combined organic layers were washed with three 25 mL portions of brine, dried over magnesium sulfate, filtered, and concentrated in vacuo to afford 3.4 g (99%) of 4-(5-fluoro-2-methoxyphenyl)-2-methoxymethoxy-4-methyl-2-trifluoromethylpentanoic acid ethyl ester which was used without further purification.
Workup
- waitAfter 15 minutes
- extractionextracted with three 25 mL portions of EtOAc
- washThe combined organic layers were washed with three 25 mL portions of brine
- dry with materialdried over magnesium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-f5f1997561cd46c8a3e25b12be531afc
- Source dataset
- uspto-grants-2007_09
- Patent number
- US07268152B2
Reaction notes
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