Pentamethylbenzene → HCID 53276190, compound

HRID 333294Notes

Reaction equation

HRID 333294 reaction equation
C(OC(=O)CC1(C(N[CH2:19][CH:20]([CH2:28][C:29]2[CH:34]=[C:33]([Cl:35])[CH:32]=[C:31]([Cl:36])[CH:30]=2)[C:21]([O:23]C(C)(C)C)=[O:22])=O)CCCC1)C1C=CC=CC=1.CC1C(C)=C(C)C(C)=C(C)C=1>C(O)(C(F)(F)F)=O.CCOC(C)=O.[Pd]>[Cl:35][C:33]1[CH:34]=[C:29]([CH:30]=[C:31]([Cl:36])[CH:32]=1)[CH2:28][CH:20]([CH3:19])[C:21]([OH:23])=[O:22]

Participants

6

Reactant 2

HCID 12784PentamethylbenzeneHCID 68754285HCID 68754285, compound

Product 1

HCID 53276190HCID 53276190, compoundYield 113.1%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 6422Trifluoroacetic acidSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tert-butyl 3-(1-(2-(benzyloxy)-2-oxoethyl)cyclopentanecarboxamido)-2-(3,5-dichlorobenzyl)propanoate (130 mg, 0.237 mmol) in TFA (1.5 ml), pentamethylbenzene (351 mg, 2.370 mmol) was added at room temperature. After stirred for 2 hr, the reaction mixture was concentrated under reduced pressure. The obtained crude material was hydrogenated under hydrogen atmosphere (1 atm) with Pd/C in EtOAc for 0.5 hr at room temperature. The reaction mixture was filtered, and the filtered cake was washed with MeOH. The combined filtrate was concentrated under reduced pressure. The obtained residue was purified by RP-HPLC (SunFire, H2O (0.1% TFA)/CH3CN) to give 341-(carboxymethyl)cyclopentanecarboxamido)-2-(3,5-dichlorobenzyl)propanoic acid (62.5 mg); Retention time=0.71 minutes (condition B); MS (m+1)=402.0; 1H NMR (400 MHz, DMSO-6, mixture of rotamers) δ ppm 1.47-1.58 (m, 6H) 1.95-2.05 (m, 2H) 2.54-2.63 (m, 2H) 2.68-2.85 (m, 3H) 3.13-3.29 (m, 2H) 7.24 (d, J=1.8 Hz, 2H) 7.42-7.43 (m, 1H) 7.60-7.63 (m, 1H); HRMS (ES+) m/z for C18H22Cl2NO5 [M+H]+ calcd 402.0875. found 402.0854

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. customThe obtained crude material
  3. customfor 0.5 hr
  4. customat room temperature
  5. filtrationThe reaction mixture was filtered
  6. washthe filtered cake was washed with MeOH
  7. concentrationThe combined filtrate was concentrated under reduced pressure
  8. customThe obtained residue was purified by RP-HPLC (SunFire, H2O (0.1% TFA)/CH3CN)

Sources & evidence

ORD record
ord-19d10d00fba246a889945dea4d05f733
Source dataset
uspto-grants-2014_11
Patent number
US08877815B2

Reaction notes

Loading…