Diisopropylethylamine → (2S,5S)-ethyl 1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-5-methylpyrrolidine-2-carboxylate

HRID 1625508Notes

Reaction equation

HRID 1625508 reaction equation
[CH3:1][C@@H:2]1[NH2+:6][C@H:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:4][CH2:3]1.[CH3:12][O:13][C:14]([NH:16][C@@H:17]([CH:21]([CH3:23])[CH3:22])[C:18](O)=[O:19])=[O:15].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O>[CH3:12][O:13][C:14]([NH:16][C@@H:17]([CH:21]([CH3:23])[CH3:22])[C:18]([N:6]1[C@@H:2]([CH3:1])[CH2:3][CH2:4][C@H:5]1[C:7]([O:9][CH2:10][CH3:11])=[O:8])=[O:19])=[O:15]

Participants

7

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 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 86311062HCID 86311062, compound

Product 1

HCID 67411636(2S,5S)-ethyl 1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-5-methylpyrrolidine-2-carboxylateYield 73%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a cold (0-4° C.) stirred solution of ethyl (2S,5S)-5-methylpyrrolidin-1-ium-2-carboxylate (7 g, 24.4 mmol) (J. Med. Chem. 2006, 49, 3520-3535), (2S)-2-(methoxycarbonylamino)-3-methyl-butanoic acid (4.5 g, 25.6 mmol), and HATU (9.7 g, 25.6 mmol) in DMF (66 ml) is added DIPEA (12.7 ml, 73.3 mmol). The resultant mixture is slowly warmed up to rt and stirred for 20 hours. The reaction mixture is diluted with water and extracted with ethyl acetate. The combined extracts are washed with sodium bicarbonate, brine, dried (Na2SO4) and concentrated. The residue is purified by flash column chromatography on silica gel using ethyl acetate-hexanes (3:7 to 4:6) as eluent to afford ethyl (2S,5S)-1-[(2S)-2-(methoxycarbonylamino)-3-methyl-butanoyl]-5-methyl-pyrrolidine-2-carboxylate (5.6 g, 73%) as a white solid.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined extracts are washed with sodium bicarbonate, brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue is purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-a01f94add5cb4b74a08b835bb8ce8dbe
Source dataset
uspto-grants-2014_07
Patent number
US08779156B2

Reaction notes

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