Ammonium Chloride → 3-Trifluoromethyl-5-(2-trimethylsilanyl-ethylsulfanyl)-benzoic acid methyl ester

HRID 403392Notes

Reaction equation

HRID 403392 reaction equation
[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[C:6](Br)[CH:5]=1.[CH3:16][Si:17]([CH3:22])([CH3:21])[CH2:18][CH2:19][SH:20].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(N(CC)C(C)C)(C)C.[Cl-].[NH4+]>O1CCOCC1.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].C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:5]=[C:6]([S:20][CH2:19][CH2:18][Si:17]([CH3:22])([CH3:21])[CH3:16])[CH:7]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:9]=1

Participants

9

Reactant 5

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 2055212-(Trimethylsilyl)ethanethiolHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 18942156Methyl 3-bromo-5-(trifluoromethyl)benzoate

Product 1

HCID 682038313-Trifluoromethyl-5-(2-trimethylsilanyl-ethylsulfanyl)-benzoic acid methyl ester

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 3-bromo-5-trifluoromethyl-benzoic acid methyl ester (600 mg, 2.12 mmol, CAS RN 187331-46-0) in dioxane (6 mL) and 2-(trimethylsilyl)ethanethiol (285 mg, 335 μL, 2.12 mmol, CAS RN 18143-30-1) was stirred under argon for 5 min., treated with tris(dibenzylideneacetone)dipalladium (0) (48.5 mg, 53.0 μmol, CAS RN 52522-40-4), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (61.3 mg, 106 μmol, xantphos, CAS RN 161265-03-8) and N,N-diisopropylethylamine (548 mg, 740 μL, 4.24 mmol) and stirred at 120° C. in a sealed tube for 4 h. Stirring was continued at room temperature for another 18 hours. The reaction mixture was poured on saturated aqueous ammonium chloride solution and ethyl acetate and the layers were separated. The aqueous layer was extracted twice with ethyl acetate. The organic layers were dried over magnesium sulfate, filtered, treated with silica gel and evaporated. The compound was purified by silica gel chromatography on a 20 g column using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethyl acetate (100:0 to 80:20). Yellow liquid (587 mg, 82%). MS (EI): m/z=336 ([M]).

Workup

  1. stirringStirring
  2. waitwas continued at room temperature for another 18 hours
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted twice with ethyl acetate
  5. dry with materialThe organic layers were dried over magnesium sulfate
  6. filtrationfiltered
  7. additiontreated with silica gel
  8. customevaporated
  9. customThe compound was purified by silica gel chromatography on a 20 g column
  10. washeluting with a gradient of n-heptane:ethyl acetate (100:0 to 80:20)

Sources & evidence

ORD record
ord-c4f1388f45074c419d819654a4094e3c
Source dataset
uspto-grants-2014_06
Patent number
US08748434B2

Reaction notes

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