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

HRID 243029Notes

Reaction equation

HRID 243029 reaction equation
C(OC([NH:8][C@@H:9]([CH2:36][CH3:37])[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]([CH2:36][CH3:37])[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]([CH3:32])([CH3:33])[CH3:34])[CH2:22]1)=[O:11]

Participants

5

Reactant 3

HCID 1140TolueneHCID 6422Trifluoroacetic acidHCID 681569832,2-Dimethylpropionic acid 2-{(R)-3-[2-((S)-2-tert-butoxycarbonylaminobutyrylamino)-5-fluorophenylamino]piperidin-1-yl}ethyl ester

Product 1

HCID 681589402,2-Dimethylpropionic acid 2-{(R)-3-[2-((S)-2-aminobutyrylamino)-5-fluorophenylamino]piperidin-1-yl}ethyl esterYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To an ice-cooled solution of 2,2-dimethylpropionic acid 2-{(R)-3-[2-((S)-2-tert-butoxycarbonylaminobutyrylamino)-5-fluorophenylamino]piperidin-1-yl}ethyl ester (0.732 g, 1.4 mmol) in DCM (25 mL) was added TFA (6 mL) and the mixture stirred at RT for 1.5 h. Toluene was added and 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 affording the title compound as a brown gum (0.59 g, 100%). LCMS (Method B): RT 1.76 min [M+H]+ 423.

Workup

  1. customvolatiles 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-d3c4bde15677426d8b9d98ebc1a9ec12
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

Loading…