(1,1'-Binaphthalen)-2-yldi-tert-butylphosphine → HCID 57666005, compound

HRID 889764Notes

Reaction equation

HRID 889764 reaction equation
[CH2:1]([O:3][C:4](=[O:34])[CH:5]([C:10]1[CH:11]=[C:12]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=2)[CH:13]=[C:14](OS(C(F)(F)F)(=O)=O)[CH:15]=1)[CH2:6][CH:7]([CH3:9])[CH3:8])[CH3:2].C(P(C(C)(C)C)C1C=CC2C(=CC=CC=2)C=1C1C2C(=CC=CC=2)C=CC=1)(C)(C)C.[CH3:64][C:65]1[CH:77]=[CH:76][CH:75]=[CH:74][C:66]=1[CH2:67][CH:68]1[CH2:73][CH2:72][CH2:71][CH2:70][NH:69]1.CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:1]([O:3][C:4](=[O:34])[CH:5]([C:10]1[CH:11]=[C:12]([C:24]2[CH:25]=[CH:26][C:27]([C:30]([F:32])([F:33])[F:31])=[CH:28][CH:29]=2)[CH:13]=[C:14]([N:69]2[CH2:70][CH2:71][CH2:72][CH2:73][CH:68]2[CH2:67][C:66]2[CH:74]=[CH:75][CH:76]=[CH:77][C:65]=2[CH3:64])[CH:15]=1)[CH2:6][CH:7]([CH3:9])[CH3:8])[CH3:2]

Participants

7

Reactant 4

HCID 2734941(1,1'-Binaphthalen)-2-yldi-tert-butylphosphineHCID 3595928HCID 3595928, compoundHCID 23676156Sodium t-butoxideHCID 577550554-Methyl-2-(5-trifluoromethanesulfonyloxy-4'-trifluoromethyl-biphenyl-3-yl)-pentanoic acid ethyl ester

Product 1

HCID 57666005HCID 57666005, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 4-methyl-2-(5-trifluoromethanesulfonyloxy-4′-trifluoromethyl-biphenyl-3-yl)-pentanoic acid ethyl ester (1g) (190 mg, 0.37 mmol) in toluene (2.5 mL) in a sealed tube was added racemic-2-(di-t-butylphosphino)-1,1′-binaphthyl (44 mg, 0.11 mmol), Pd(OAc)2 (83 mg, 0.37 mmol), 2-(2-methyl-benzyl)-piperidine (98 mg, 0.52 mmol). The system was flushed with nitrogen. To this was added NaOtBu (53 mg, 0.56 mmol) and heated to 100° C. for 1 h. The reaction was cooled to room temperature and quenched by slow addition of water. The mixture was extracted with EtOAc (3×20 mL). The organic phase was washed with saturated NaHCO3 solution and brine. The organic fraction was dried (MgSO4) and concentrated in vacuo. The crude mixture was purified by ISCO column chromatography to obtain 4-methyl-2-{5-[2-(2-methyl-benzyl)-piperidin-1-yl]-4′-trifluoromethyl-biphenyl-3-yl}-pentanoic acid ethyl ester. Calcd for C34H40F3NO2 (M+H) 552.68, Found 552.41.

Workup

  1. customThe system was flushed with nitrogen
  2. temperatureThe reaction was cooled to room temperature
  3. customquenched by slow addition of water
  4. extractionThe mixture was extracted with EtOAc (3×20 mL)
  5. washThe organic phase was washed with saturated NaHCO3 solution and brine
  6. dry with materialThe organic fraction was dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe crude mixture was purified by ISCO column chromatography

Sources & evidence

ORD record
ord-13e223d679194c3c94918b2066c2022f
Source dataset
uspto-grants-2012_08
Patent number
US08252935B2

Reaction notes

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