Ethyl 4-iodobenzoate → Ethyl(+/-)-4-(4,4,4-trifluoro-1-hydroxybutyl)benzoate

HRID 537572Notes

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

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, 1.3M in tetrahydrofuran) dropwise. The mixture was stirred for approximately 1 hour whereupon the 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 1.0M hydrochloric acid and the aqueous layer was extracted with ethyl acetate (3×). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. The alcohol was used without further purification.

Workup

additionwas added dropwise
temperatureslowly warmed to ambient temperature over 12 hours
customThe reaction was quenched with aqueous 1.0M hydrochloric acid
extractionthe aqueous layer was extracted with ethyl acetate (3×)
dry with materialThe combined organic layers were dried over magnesium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe alcohol was used without further purification

Sources & evidence

ORD record: ord-7d733c55b4ff489bbf1838aa99db69ec
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08859591B2

Reaction notes

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