Sodium ethanethiolate → (R)-N-[2-Chloro-4-(ethylsulphanyl)phenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide

HRID 1062384Notes

Reaction equation

[CH2:1]([S-:3])[CH3:2].[Na+].[Cl:5][C:6]1[CH:11]=[C:10](I)[CH:9]=[CH:8][C:7]=1[NH:13][C:14](=[O:22])[C@:15]([OH:21])([CH3:20])[C:16]([F:19])([F:18])[F:17]>N1C2C(=CC=CC=2)C=CC=1.N1C=CC=CC=1.C(OCC)(=O)C.[Cu]Cl>[Cl:5][C:6]1[CH:11]=[C:10]([S:3][CH2:1][CH3:2])[CH:9]=[CH:8][C:7]=1[NH:13][C:14](=[O:22])[C@:15]([OH:21])([CH3:20])[C:16]([F:19])([F:18])[F:17]

Participants

Conditions

Temperature: 200 °C

Procedure

Copper (I) chloride (0.5 g) and sodium ethanethiolate (0.54 g) were added sequentially to a deoxygenated solution of (R)-N-(2-chloro-4-iodophenyl)-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide (Example 197) (2.0 g) in quinoline (6 ml) and pyridine (1.5 ml). The mixture was heated to 200° C. under argon for 18 hours, cooled dissolved in ethyl acetate (200 ml), washed with dilute aqueous hydrochloric acid (2×100 ml) and brine (2×50 ml) and then dried. Volatile material was removed by evaporation and the residue was purified by chromatography on silica gel eluting with 10-40% ethyl acetate/iso-hexane to give the title compound as a gum (1.4 g). NMR (CDCl3): 1.29 (t, 3H), 1.57 (s, 3H), 2.91 (q, 2H), 3.69 (s, 1H), 7.24 (d, 1H), 7.35 (s, 1H), 8.24 (d, 1H), 8.77 (s, 1H); MS (ESP−): 326.

Workup

temperaturecooled
washwashed with dilute aqueous hydrochloric acid (2×100 ml) and brine (2×50 ml)
customdried
customVolatile material was removed by evaporation
customthe residue was purified by chromatography on silica gel eluting with 10-40% ethyl acetate/iso-hexane

Sources & evidence

ORD record: ord-4e379053cd7c4ada8547bd625b16720d
Source dataset: uspto-grants-2005_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06960688B2

Reaction notes

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