Diisopropylethylamine → (2S,4R)-tert-butyl 4-(benzyloxycarbonylamino)-2-(4-(4-fluorophenoxy)phenylcarbamoyl)pyrrolidine-1-carboxylate

HRID 1630080Notes

Reaction equation

HRID 1630080 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:16][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C@H:14]([C:24]([OH:26])=O)[CH2:13]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C(ON1N=N[C:37]2[CH:38]=[CH:39][CH:40]=[N:41][C:36]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:51][C:52]1[CH:65]=[CH:64][C:55]([O:56]NC2C=CC=CC=2)=[CH:54][CH:53]=1.[CH3:66]CN(C(C)C)C(C)C>CN(C=O)C>[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:16][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C@H:14]([C:24](=[O:26])[NH:41][C:36]2[CH:37]=[CH:38][C:39]([O:56][C:55]3[CH:64]=[CH:65][C:52]([F:51])=[CH:53][CH:54]=3)=[CH:40][CH:66]=2)[CH2:13]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11660571(2S,4R)-4-(((benzyloxy)carbonyl)amino)-1-((tert-butoxy)carbonyl)pyrrolidine-2-carboxylic acidHCID 536486284-Fluorophenoxyaniline

Product 1

HCID 67009501(2S,4R)-tert-butyl 4-(benzyloxycarbonylamino)-2-(4-(4-fluorophenoxy)phenylcarbamoyl)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Step (b) A flask was charged with (2S,4R)-4-(benzyloxycarbonylamino)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid (2.51 g, 6.86 mmol), HATU (2.87 g, 7.55 mmol), 4-fluorophenoxyaniline (1.41 g, 6.86 mmol), DIEA (5.0 mL, 29 mmol) and DMF (20 mL). The reaction mixture was stirred at ambient temperature for 30 minutes and then quenched with saturated sodium bicarbonate (aq., 20 mL). The mixture was extracted with ethyl acetate (60 mL) and the extract was washed with deionized water (30 mL) and then brine (30 mL), dried over anhydrous sodium sulfate, filtered and concentrated to give (2S,4R)-tert-butyl 4-(benzyloxycarbonylamino)-2-(4-(4-fluorophenoxy)phenylcarbamoyl)pyrrolidine-1-carboxylate as a crude mixture which was carried forward without further purification.

Workup

  1. customquenched with saturated sodium bicarbonate (aq., 20 mL)
  2. extractionThe mixture was extracted with ethyl acetate (60 mL)
  3. washthe extract was washed with deionized water (30 mL)
  4. dry with materialbrine (30 mL), dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-4c160b8468ce4d93ab463d31c4994136
Source dataset
uspto-grants-2014_07
Patent number
US08791102B2

Reaction notes

Loading…