Toluene → 2,2-Dimethylpropionic acid 2-{(R)-3-[2-((S)-2-aminopropionylamino)-5-fluorophenylamino]piperidin-1-yl}ethyl ester

HRID 243026Notes

Reaction equation

HRID 243026 reaction equation
C(OC([NH:8][C@@H:9]([CH3:36])[C:10]([NH:12][C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=1[NH:20][C@@H:21]1[CH2:26][CH2:25][CH2:24][N:23]([CH2:27][CH2:28][O:29][C:30](=[O:35])[C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:22]1)=[O:11])=O)(C)(C)C.C(O)(C(F)(F)F)=O.C1(C)C=CC=CC=1>C(Cl)Cl>[NH2:8][C@@H:9]([CH3:36])[C:10]([NH:12][C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=1[NH:20][C@@H:21]1[CH2:26][CH2:25][CH2:24][N:23]([CH2:27][CH2:28][O:29][C:30](=[O:35])[C:31]([CH3:33])([CH3:32])[CH3:34])[CH2:22]1)=[O:11]

Participants

5

Reactant 3

HCID 1140TolueneHCID 6422Trifluoroacetic acidHCID 681578402,2-Dimethylpropionic acid 2-{(R)-3-[2-((S)-2-tert-butoxycarbonylaminopropionylamino)-5-fluoro-phenylamino]piperidin-1-yl}ethyl ester

Product 1

HCID 681590572,2-Dimethylpropionic acid 2-{(R)-3-[2-((S)-2-aminopropionylamino)-5-fluorophenylamino]piperidin-1-yl}ethyl esterYield 84.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To an ice-cooled solution of 2,2-dimethylpropionic acid 2-{(R)-3-[2-((S)-2-tert-butoxycarbonylaminopropionylamino)-5-fluorophenylamino]-piperidin-1-yl}ethyl ester (0.74 mmol) in DCM (20 mL) was added TFA (5 mL) and the mixture stirred at RT for 1.5 h. Toluene was added and volatiles were removed in vacuo. The resulting residue was dissolved in MeOH and loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the product eluted with 0.5M NH3/MeOH. The product containing fractions were combined and concentrated in vacuo affording the title compound as a purple oil (0.255 g, 84% over 2 steps). LCMS (Method J): RT 1.65 min [M+H]+ 409.

Workup

  1. customvolatiles were removed in vacuo
  2. dissolutionThe resulting residue was dissolved in MeOH
  3. washThe cartridge was washed with MeOH
  4. washthe product eluted with 0.5M NH3/MeOH
  5. additionThe product containing fractions
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9023d9ccb61245ba9cd04c151b1e43e6
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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