2-Methylpiperidine → HCID 57666047, compound

HRID 889689Notes

Reaction equation

HRID 889689 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][CH:65]1[CH2:70][CH2:69][CH2:68][CH2:67][NH:66]1.CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.CC(O)=O.CC(O)=O.[Pd]>[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:66]2[CH2:67][CH2:68][CH2:69][CH2:70][CH:65]2[CH3:64])[CH:15]=1)[CH2:6][CH:7]([CH3:9])[CH3:8])[CH3:2]

Participants

7

Reactant 4

HCID 79742-Methylpiperidine2×HCID 2734941(1,1'-Binaphthalen)-2-yldi-tert-butylphosphineHCID 23676156Sodium t-butoxide2×HCID 577550554-Methyl-2-(5-trifluoromethanesulfonyloxy-4'-trifluoromethyl-biphenyl-3-yl)-pentanoic acid ethyl ester

Product 1

HCID 57666047HCID 57666047, compound

Reagents, catalysts & solvents 2

HCID 4144353Palladium (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 (63 mg, 0.12 mmol) in toluene (1 mL) in a sealed tube was added racemic-2-(di-t-butylphosphino)-1,1′-binaphthyl (48 mg, 0.12 mmol), Pd(O AC)2 (27 mg, 0.12 mmol), 2-methyl-piperidine (0.020 mL, 0.17 mmol). The system was flushed with nitrogen. To this was added NaOtBu (14 mg, 0.14 mmol) and heated to 100° C. for 10 minutes. The reaction was cooled to room temperature. To this was added another portion of Pd(OAC)2 (27 mg, 0.12 mmol), 2-methyl-piperidine (0. 020 mL, 0.17 mmol) and NaOtBu (14 mg, 0.14 mmol). The system was heated to 100° C. for 5 minutes, 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-methyl-piperidin-1-yl)-4′-trifluoromethyl-biphenyl-3-yl]-pentanoic acid ethyl ester. Calcd for C27H34F3NO2 (M+H) 462.56, Found 462.3.

Workup

  1. customThe system was flushed with nitrogen
  2. temperatureThe reaction was cooled to room temperature
  3. temperatureThe system was heated to 100° C. for 5 minutes
  4. temperaturecooled to room temperature
  5. customquenched by slow addition of water
  6. extractionThe mixture was extracted with EtOAc (3×20 mL)
  7. washThe organic phase was washed with saturated NaHCO3 solution and brine
  8. dry with materialThe organic fraction was dried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customThe crude mixture was purified by ISCO column chromatography

Sources & evidence

ORD record
ord-ef1859a0c9554ffd80bab18d0110f4db
Source dataset
uspto-grants-2012_08
Patent number
US08252935B2

Reaction notes

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