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

HRID 1630071Notes

Reaction equation

HRID 1630071 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([OH:13])[CH2:10][C@H:9]1[C:14]([OH:16])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:41][C:42]1[CH:55]=[CH:54][C:45]([O:46][C:47]2[CH:53]=[CH:52][C:50]([NH2:51])=[CH:49][CH:48]=2)=[CH:44][CH:43]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[F:41][C:42]1[CH:55]=[CH:54][C:45]([O:46][C:47]2[CH:53]=[CH:52][C:50]([NH:51][C:14]([C@@H:9]3[CH2:10][C@@H:11]([OH:13])[CH2:12][N:8]3[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[O:16])=[CH:49][CH:48]=2)=[CH:44][CH:43]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 88804(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acidHCID 147633Benzenamine, 4-(4-fluorophenoxy)-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 67010572(2S,4R)-tert-butyl 2-(4-(4-fluorophenoxy)phenylcarbamoyl)-4-hydroxypyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Step (a) A flask was charged with (2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid (2.1 g, 9.1 mmol), HATU (3.80 g, 10.0 mmol), 4-(4-fluorophenoxy)aniline (1.85 g, 9.09 mmol), DIEA (4.8 mL, 27 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 crude (2S,4R)-tert-butyl 2-(4-(4-fluorophenoxy)phenylcarbamoyl)-4-hydroxypyrrolidine-1-carboxylate, 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-c42665e3ff78450884cfa25e34ad041c
Source dataset
uspto-grants-2014_07
Patent number
US08791102B2

Reaction notes

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