Cesium carbonate → HCID 67403211, compound

HRID 906201Notes

Reaction equation

HRID 906201 reaction equation
[C:1]([C:3]1[C:12](I)=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[C:5]([C:14]([F:17])([F:16])[F:15])[CH:4]=1)#[N:2].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+].[C@H:66]([NH2:70])([CH2:68][CH3:69])[CH3:67]>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@H:66]([NH:70][C:12]1[C:3]([C:1]#[N:2])=[CH:4][C:5]([C:14]([F:17])([F:16])[F:15])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8])([CH2:68][CH3:69])[CH3:67]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 2724537(R)-sec-butylamineHCID 67404112HCID 67404112, compound

Product 1

HCID 67403211HCID 67403211, compoundYield 31%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
95 °C

Procedure

Methyl 4-cyano-5-iodo-2-(trifluoromethyl)benzoate (174 mg, 0.49 mmol) was dissolved in dioxane (2 mL) and was sparged with nitrogen for 15 minutes. XANTPHOS (57 mg, 0.098 mmol), cesium carbonate (350 mg, 1.07 mmol), (R)-sec-butylamine (0.1 mL, 0.986 mmol), and tris(dibenzylideneacetone)dipalladium (45 mg, 0.049 mmol) were added, and the mixture was stirred in a sealed tube at 95° C. for 20 h. The reaction mixture was cooled to ambient temperature and was filtered through celite. The filter cake was washed with ethyl acetate and the filtrate was concentrated to afford an orange oil which was purified by column chromatography (silica gel, 5-15% ethyl acetate in hexanes) to afford (R)-methyl 5-(sec-butylamino)-4-cyano-2-(trifluoromethyl)benzoate (45 mg, 0.150 mmol, 31% yield) as a yellow oil. GCMS for C14H15F3N2O2: 300 (M+).

Workup

  1. customwas sparged with nitrogen for 15 minutes
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. filtrationwas filtered through celite
  4. washThe filter cake was washed with ethyl acetate
  5. concentrationthe filtrate was concentrated
  6. customto afford an orange oil which
  7. customwas purified by column chromatography (silica gel, 5-15% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-62d0fffb795f426990070957ddbf235c
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

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