Aniline → (R)-N-[2-Chloro-4-(N-phenylcarbamoyl)phenyl]-2-hydroxy-2methyl-3,3,3-trifluoropropanamide

HRID 2301043Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[CH:4][C:3]=1[NH:9][C:10](=[O:18])[C@:11]([OH:17])([CH3:16])[C:12]([F:15])([F:14])[F:13].[NH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(N(CCCC)CCCC)CCC.[C:39](OCC)(=[O:41])C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[C:6]([C:39](=[O:41])[NH:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:5]=[CH:4][C:3]=1[NH:9][C:10](=[O:18])[C@:11]([OH:17])([CH3:16])[C:12]([F:15])([F:14])[F:13]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of (R)-N-(2-chloro-4-iodophenyl)-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide (Example 197) (0.35 g), aniline (0.117 ml), tributylamine (0.232 ml) and dichlorobis-(triphenylphosphine)palladium(II) (0.009 g) was heated at 100° C. under an atmosphere of carbon monoxide for 4 hours. Ethyl acetate (10 ml) was added and the mixture was washed with water and brine then was dried. Volatile material was removed by evaporation and the residue was purified by chromatography on a silica gel Mega Bond Elut column eluting with 5-50% ethyl acetate/hexane followed by passing through a Varian Isolute SCX column to give the title compound (0.17 g) as a solid. NMR: 1.6 (s, 3H), 7.1 (t, 1H), 7.35 (t, 2H), 7.75 (d, 2H), 7.92 (s, 1H), 7.98 (dd, 1H), 8.12 (s, 1H), 8.2 (d, 1H), 9.8 (s, 1H), 10.26 (brs, 1H); MS (ESP−): 386.

Workup

washthe mixture was washed with water and brine
customthen was dried
customVolatile material was removed by evaporation
customthe residue was purified by chromatography on a silica gel Mega Bond Elut column
washeluting with 5-50% ethyl acetate/hexane

Sources & evidence

ORD record: ord-b54edcdbf03f4db3b620f2947b2dc358
Source dataset: uspto-grants-2002_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06498275B1

Reaction notes

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