Thiophenol → (R)-4-chloro-N-(1-(3-chlorophenyl)ethyl)-3-(phenylthio)benzamide

HRID 1801575Notes

Reaction equation

HRID 1801575 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][C:19]=1[Cl:20])[C:5]([NH:7][C@@H:8]([C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=1)[CH3:9])=[O:6].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.[C:63]1([SH:69])[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1.C(N(C(C)C)C(C)C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Cl:20][C:19]1[CH:18]=[CH:17][C:4]([C:5]([NH:7][C@@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[CH3:9])=[O:6])=[CH:3][C:2]=1[S:69][C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1

Participants

7

Reactant 4

HCID 7969ThiophenolHCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 59803174(R)-3-bromo-4-chloro-N-(1-(3-chlorophenyl)ethyl)benzamide

Product 1

HCID 59803178(R)-4-chloro-N-(1-(3-chlorophenyl)ethyl)-3-(phenylthio)benzamideYield 92.3%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a mixture of (R)-3-bromo-4-chloro-N-(1-(3-chlorophenyl)ethyl)benzamide 32 (0.634 g, 1.7 mmol), Pd2(dba)3 (0.100 g, 0.11 mmol), and 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (0.125 g, 0.22 mmol) was added benzenethiol (0.173 mL, 1.7 mmol), dioxane (4.5 mL) and N-ethyl-N-isopropylpropan-2-amine (0.590 mL, 3.4 mmol). The reaction mixture was degassed and heated to reflux. After 18 h, the reaction mixture was diluted with EtOAc, washed with water (1×), brine (1×), dried over MgSO4, filtered, and concentrated in vacuo. Purification by flash column chromatography on silica gel (eluted with 5% to 30% EtOAc in hexanes) gave (R)-4-chloro-N-(1-(3-chlorophenyl)ethyl)-3-(phenylthio)benzamide 33 (0.631 g, 92% yield) as a white solid. Mass spectrum: calculated for C21H17Cl2NOS 401.0. found 402.1 (M++1).

Workup

  1. customThe reaction mixture was degassed
  2. temperatureheated to reflux
  3. additionthe reaction mixture was diluted with EtOAc
  4. washwashed with water (1×), brine (1×)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by flash column chromatography on silica gel (eluted with 5% to 30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-91e3069e63ec4d3bb34b971450be79c1
Source dataset
uspto-grants-2013_01
Patent number
US08349831B2

Reaction notes

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