(1,1'-Binaphthalen)-2-yldi-tert-butylphosphine → 4-Methyl-2-[5-(2-propyl-piperidin-1-yl)-4'-trifluoromethyl-biphenyl-3-yl]-pentanoic acid ethyl ester

HRID 889685Notes

Reaction equation

HRID 889685 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.Br.[CH2:65]([CH:68]1[CH2:73][CH2:72][CH2:71][CH2:70][NH:69]1)[CH2:66][CH3:67].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[CH2:65][CH2:66][CH3:67])[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 23676156Sodium t-butoxideHCID 247209702-Propylpiperidine hydrobromideHCID 577550554-Methyl-2-(5-trifluoromethanesulfonyloxy-4'-trifluoromethyl-biphenyl-3-yl)-pentanoic acid ethyl ester

Product 1

HCID 576659754-Methyl-2-[5-(2-propyl-piperidin-1-yl)-4'-trifluoromethyl-biphenyl-3-yl]-pentanoic acid ethyl ester

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, 1 g (250 mg, 0.49 mmol) in toluene (5 mL) in a sealed tube was added racemic-2-(di-t-butylphosphino)-1,1′-binaphthyl (59 mg, 0.15 mmol), Pd(OAc)2 (110 mg, 0.49 mmol), 2-propyl-piperidine hydrogen bromide (152 mg, 0.73 mmol). The system was flushed with nitrogen. To this was added NaOtBu (118 mg, 1.23 mmol) and heated to 100° C. for 3 h. The system 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-propyl-piperidin-1-yl)-4′-trifluoromethyl-biphenyl-3-yl]-pentanoic acid ethyl ester. Calcd for C29H38F3NO2 (M+H) 490.61, Found 490.4.

Workup

  1. customThe system was flushed with nitrogen
  2. temperatureThe system 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-5a34ee1241a249c2a32261f3ff6d376a
Source dataset
uspto-grants-2012_08
Patent number
US08252935B2

Reaction notes

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