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

HRID 243036Notes

Reaction equation

HRID 243036 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 681571232,2-Dimethylpropionic acid 2-{(S)-3-[2-((S)-2-tert-butoxycarbonylaminopropionylamino)-5-fluorophenylamino]piperidin-1-yl}ethyl ester

Product 1

HCID 681573042,2-Dimethylpropionic acid 2-{(S)-3-[2-((S)-2-aminopropionylamino)-5-fluorophenylamino]piperidin-1-yl}ethyl esterYield 87.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To an ice-cooled solution of 2,2-dimethylpropionic acid 2-{(S)-3-[2-((S)-2-tert-butoxycarbonylaminopropionylamino)-5-fluorophenylamino]piperidin-1-yl}ethyl ester (2.054 g, 4.04 mmol) in DCM (40 mL) was added TFA (14 mL) and the mixture stirred at RT for 1.5 h. Toluene was added and the volatiles 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. The resulting residue was purified by column chromatography (Si—PCC, gradient 2-10% 2M NH3/MeOH in DCM) affording the title compound as a purple oil (1.443 g, 87%). LCMS (Method B): RT 1.60 min [M+H]+ 409.

Workup

  1. customthe volatiles 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
  7. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 2-10% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-10cce094b3b240c082d6bbd925772e6b
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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