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

HRID 1062395Notes

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].[SH:19][CH2:20][CH2:21][OH:22].C[O-].[Na+]>N1C=CC=CC=1.N1C2C(=CC=CC=2)C=CC=1.C(OCC)(=O)C.[Cu]Cl>[Cl:1][C:2]1[CH:7]=[C:6]([S:19][CH2:20][CH2:21][OH:22])[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: 190 °C

Procedure

A solution of (R)-N-[2-chloro-4-iodophenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide (Example 197) (0.8 g) in pyridine (1 ml) was added to a deoxygenated solution of 2-mercaptoethanol (0.18 ml), sodium methoxide (0.14 g) and copper (I) chloride (0.2 g) in quinoline (2 ml) and pyridine (2 ml). The mixture was heated to 190° C. under argon for 18 hours. The mixture was allowed to cool to room temperature then dissolved in ethyl acetate (100 ml), washed with dilute aqueous hydrochloric acid (2×50 ml) and brine (2×50 ml) then dried. Volatile material was removed by evaporation and the residue was purified by chromatography on a silica gel Mega Bond Elut column eluting with 10-60% ethyl acetate/iso-hexane to give the title compound as a gum. NMR (CDCl3): 1.76 (s, 3H), 3.10 (t, 2H), 3.75-80 (m, 2H), 7.31-7.34 (m, 1H), 7.47 (s, 1H), 8.31 (d, 1H), 8.86 (s, 1H); MS (ESP−): 342.

Workup

temperatureto cool to room temperature
washwashed with dilute aqueous hydrochloric acid (2×50 ml) and brine (2×50 ml)
customthen dried
customVolatile material was removed by evaporation
customthe residue was purified by chromatography on a silica gel Mega Bond Elut column
washeluting with 10-60% ethyl acetate/iso-hexane

Sources & evidence

ORD record: ord-379c39ef300b41cf98f4df886dbcdcd0
Source dataset: uspto-grants-2005_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06960688B2

Reaction notes

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