Hydrogen Bromide → 2-(4-Hydroxyphenyl)-3-methylbutyric acid
Reaction equation
C[O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]#N)=[CH:5][CH:4]=1.[CH:12](Br)([CH3:14])[CH3:13].Br.[OH-:17].[Na+].[OH2:19].C1(C)C=CC=CC=1>>[CH:12]([CH:9]([C:6]1[CH:7]=[CH:8][C:3]([OH:2])=[CH:4][CH:5]=1)[C:10]([OH:19])=[O:17])([CH3:14])[CH3:13]Participants
Procedure
53.1 g of p-methoxyphenylacetonitrile was alkylated with 51.4 g of isopropyl bromide in NaOH/H2O/toluene/Aliquot 336 at reflux for 24 hours. (See, for example, U.S. Pat. Nos. 4,056,509 and 4,144,264.) The crude product was hydrolyzed and demethylated in refluxing concentrated HBr to give α-isopropyl 4-hydroxyphenylacetic acid at 69% overall yeild. The hydroxy acid was alkylated with chlorodifluoromethane in the presence of sodium hydroxide and water according to the procedure set forth at page 2 of British Patent Application No. 2017668A to give crude α-isopropyl-4-difluoromethoxyphenylacetic acid at 62 wt%. 15.9 g of this acid was then reacted with 18.7 g of α-cyano-3-phenoxybenzyl bromide in a mixed solvent of sodium carbonate, water and toluene for 4 hours at 70° C. to give crude difluoromethoxy ester. This ester was purified by chromatography on a silica gel column to yield the final product having an isomer pair ratio of about 50/50.
Workup
- temperatureat reflux for 24 hours
Sources & evidence
- ORD record
- ord-6b72f95751034774be424aae5ac4aaa2
- Source dataset
- uspto-grants-1981_12
- Patent number
- US04307036
Reaction notes
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