Trichloroacetonitrile → Trichloroacetimidic acid (S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl ester

HRID 2377026Notes

Reaction equation

[F:1][C:2]([F:17])([F:16])[C:3]1[CH:4]=[C:5]([C@@H:13]([OH:15])[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C1CCN2C(=NCCC2)CC1.[Cl:29][C:30]([Cl:34])([Cl:33])[C:31]#[N:32]>C(OCC)C>[F:1][C:2]([F:16])([F:17])[C:3]1[CH:4]=[C:5]([C@@H:13]([O:15][C:31](=[NH:32])[C:30]([Cl:34])([Cl:33])[Cl:29])[CH3:14])[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 25.82 g (100 mmol) of (1S)-1-[3,5-bis(trifluoromethyl)phenyl]ethanol in 200 mL dry diethyl ether under nitrogen atmosphere was cooled in an ice/water bath. Neat 3 mL (20 mmol, 0.2 equiv) DBU was added to the reaction flask then the mixture was stirred at 0° C. for ten min. Slowly 15 mL (150 mmol, 1.5 equiv.) trichloroacetonitrile was added dropwise over 15 min. The reaction was stirred at 0° C. for 2 hr. during which time it became deep yellow in color. The volatiles were removed under vacuum using a cool bath (<35° C.) to give a pale brown mobile liquid which was purified by column chromatography on silica gel (3″×10″ pad) in two batches eluting with hexanes/EtOAc (9/1) then hexanes/EtOAc (4/1). The product fractions were combined and the solvent removed under vacuum to give the title compound as a pale yellow oil. 1H-NMR (CDCl3): δ: 1.74 (d, 3H, 6.5 Hz), 6.07 (q, 1H, 6.5 Hz), 7.82 (s, 1H), 7.86 (s, 2H), 8.40 (br. s, 1H) ppm.

Workup

stirringThe reaction was stirred at 0° C. for 2 hr
customThe volatiles were removed under vacuum
custom(<35° C.)
customto give a pale brown mobile liquid which
customwas purified by column chromatography on silica gel (3″×10″ pad) in two batches
washeluting with hexanes/EtOAc (9/1)
customthe solvent removed under vacuum

Sources & evidence

ORD record: ord-eb7fc64f822248f5ba426fe31af6a819
Source dataset: uspto-grants-2008_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07468437B2

Reaction notes

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