Ethyl 4-iodobenzoate → Ethyl(+/-)-4-(4,4,4-trifluoro-1-hydroxybutyl)benzoate
Reaction equation
I[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=1.[Cl-].[Li+].C([Mg]Cl)(C)C.[F:20][C:21]([F:27])([F:26])[CH2:22][CH2:23][CH:24]=[O:25]>O1CCCC1>[F:20][C:21]([F:27])([F:26])[CH2:22][CH2:23][CH:24]([C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=1)[OH:25]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -40 °C
Procedure
To a solution of the ethyl 4-iodobenzoate (1.21 ml, 7.24 mmol) in tetrahydrofuran (12 ml) at −40° C. was added isopropylmagnesium chloride lithium chloride complex (6.13 ml, 7.97 mmol, 1.3 M in tetrahydrofuran) dropwise. The mixture was stirred for approximately 1 hour whereupon 4,4,4-trifluorobutanal (0.761 ml, 0.724 mmol) was added dropwise. The mixture was stirred at −40° C. for 15 minutes and slowly warmed to ambient temperature over 12 hours. The reaction was quenched with aqueous 1.0 M hydrochloric acid, and the aqueous layer was extracted with ethyl acetate (3×). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated under reduced pressure to give ethyl (+/−)-4-(4,4,4-trifluoro-1-hydroxybutyl)benzoate, which was used without further purification.
Workup
- additionwas added dropwise
- temperatureslowly warmed to ambient temperature over 12 hours
- customThe reaction was quenched with aqueous 1.0 M hydrochloric acid
- extractionthe aqueous layer was extracted with ethyl acetate (3×)
- dry with materialThe combined organic layers were dried over magnesium sulfate
- filtrationfiltered
- concentrationconcentrated under reduced pressure
Sources & evidence
- ORD record
- ord-cf91dcdb766542f0bbfe46e22b7d4d46
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09139538B2
Reaction notes
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