Lawesson's reagent → (R)-4-fluoro-N-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-3-(trifluoromethyl)benzothioamide

HRID 1712794Notes

Reaction equation

HRID 1712794 reaction equation
[F:1][C:2]1[CH:39]=[CH:38][C:5]([C:6]([NH:8][C@@:9]([C:24]2[CH:29]=[C:28]([O:30][C:31]([F:36])([F:35])[CH:32]([F:34])[F:33])[CH:27]=[C:26]([F:37])[CH:25]=2)([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=O)=[CH:4][C:3]=1[C:40]([F:43])([F:42])[F:41].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:53])=CC=1>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:39]=[CH:38][C:5]([C:6](=[S:53])[NH:8][C@@:9]([C:24]2[CH:29]=[C:28]([O:30][C:31]([F:36])([F:35])[CH:32]([F:34])[F:33])[CH:27]=[C:26]([F:37])[CH:25]=2)([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:4][C:3]=1[C:40]([F:43])([F:42])[F:41]

Participants

4

Reactant 2

HCID 87949Lawesson's reagentHCID 23582278(R)-4-fluoro-N-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-3-(trifluoromethyl)benzamide

Product 1

HCID 59459064(R)-4-fluoro-N-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-3-(trifluoromethyl)benzothioamideYield 83%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a stirred solution of (R)-4-fluoro-N-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-3-(trifluoromethyl)benzamide (105 mg, 0.17 mmol), prepared as described in Procedure 3, 4, 5, 6 and 7, in toluene (5.2 mL) was added Lawesson's reagent (83 mg, 0.20 mmol). The reaction mixture was heated at 110° C. After 8 h, the reaction mixture was concentrated and the residue was purified by ISCO column chromatography (EtOAc/hexane 0-100%, SiO2) to provide (R)-4-fluoro-N-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-3-(trifluoromethyl)benzothioamide (Example 315, 89 mg, 83% yield) as a yellow oil. 1H NMR (500 MHz, CDCl3) δ ppm 7.92 (s, 1H), 7.74-7.72 (m, 1H), 7.68-7.66 (m, 1H), 7.22-6.86 (m, 11H), 6.72 (d, J=5 Hz, 2H), 5.92-5.70 (m, 1H), 4.36 (d, J=15 Hz, 1H), 3.82 (d, J=10 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ ppm 195 (C═S); LC/MS: RT=4.393 min [M+H] 632.4 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeCN/H2O over 4 minutes containing 0.1% NH4OAc; 4 mL/min, monitoring at 220 nm).

Workup

  1. concentrationthe reaction mixture was concentrated
  2. customthe residue was purified by ISCO column chromatography (EtOAc/hexane 0-100%, SiO2)

Sources & evidence

ORD record
ord-c5a091b945ab4ee1a1ac040eadd923d1
Source dataset
uspto-grants-2010_09
Patent number
US07790770B2

Reaction notes

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