Thionyl Chloride → N-(4'-chloro-2'-fluoro-5'-isopropyloxyphenyl)-5-chloro-3-(trifluoromethyl)pentanamide

HRID 2255172Notes

Reaction equation

[Cl:1][C:2]1[C:7]([O:8][CH:9]([CH3:11])[CH3:10])=[CH:6][C:5]([NH:12][C:13](=[O:23])[CH2:14][CH:15]([C:19]([F:22])([F:21])[F:20])[CH2:16][CH2:17]O)=[C:4]([F:24])[CH:3]=1.S(Cl)([Cl:27])=O>C(Cl)Cl>[Cl:1][C:2]1[C:7]([O:8][CH:9]([CH3:11])[CH3:10])=[CH:6][C:5]([NH:12][C:13](=[O:23])[CH2:14][CH:15]([C:19]([F:22])([F:21])[F:20])[CH2:16][CH2:17][Cl:27])=[C:4]([F:24])[CH:3]=1

Participants

Conditions

Temperature: 40 °C

Procedure

To a solution of N-(4'-chloro-2'-fluoro-5'-isopropyloxyphenyl)-5-hydroxy-3-(trifluoromethyl)pentanamide (1.2 g, 3.2 mmol) (Compound 45) in methylene chloride (100 ml), was added thionyl chloride (0.24 ml) in one portion via pipette. The solution turned brown. The reaction mixture was heated to 40°-50° C. for 7 hours, kept at room temperature for 64 hours, heated to 40° C. for 3 hours, and then stirred at room temperature for 18 hours. Then additional thionyl chloride (0.1 ml) was added and the reaction mixture was heated to 40° C. for 4 more hours. After cooling, the solvent was removed in vacuo and the resulting golden brown, semi-solid product mixture was purified via flash chromatography (20 ml fractions, 2'×7' column, 1:9 ethyl acetate/hexanes) to yield a brown solid, m.p. of 57°-63° C.

Workup

temperatureThe reaction mixture was heated to 40°-50° C. for 7 hours
temperaturethe reaction mixture was heated to 40° C. for 4 more hours
temperatureAfter cooling
customthe solvent was removed in vacuo
customthe resulting golden brown, semi-solid product mixture was purified via flash chromatography (20 ml fractions, 2'×7' column, 1:9 ethyl acetate/hexanes)
customto yield a brown solid, m.p. of 57°-63° C.

Sources & evidence

ORD record: ord-82548973644144cdb0af6eac82a94e9c
Source dataset: uspto-grants-1993_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05238908

Reaction notes

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