Triethylamine → L-Proline, N-(methoxycarbonyl)-L-valyl-4-hydroxy-, methyl ester, (4R)-

HRID 1504308Notes

Reaction equation

HRID 1504308 reaction equation
[CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][C@@H:8]([OH:10])[CH2:7][NH:6]1)=[O:4].[CH3:11][O:12][C:13]([NH:15][C@@H:16]([CH:20]([CH3:22])[CH3:21])[C:17](O)=[O:18])=[O:14].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>C(Cl)Cl>[CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][C@@H:8]([OH:10])[CH2:7][N:6]1[C:17](=[O:18])[C@@H:16]([NH:15][C:13]([O:12][CH3:11])=[O:14])[CH:20]([CH3:22])[CH3:21])=[O:4]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 7015125(4R)-4-Hydroxy-L-proline methyl esterHCID 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 acid

Product 1

HCID 58313116L-Proline, N-(methoxycarbonyl)-L-valyl-4-hydroxy-, methyl ester, (4R)-

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (2S,4R)-4-hydroxy-pyrrolidine-2-carboxylic acid methyl ester in dry DCM (200 mL) was added (S)-2-methoxycarbonylamino-3-methyl-butyric acid (10 g, 55 mmol), HATU (24 g, 63.25 mmol), and triethylamine (16.7 g, 165 mmol. The reaction mixture was stirred at RT overnight. DCM (200 mL) was added and the solution was washed with brine, dried, concentrated and purified by silica gel column chromatography (eluted with petroleum ether:EtOAc 10:1 to 1:4)) to give the title intermediate as a yellow oil (20 g). (m/z): [M+H]+ calcd for C13H22N2O6 303.15. found 303.1.

Workup

  1. washthe solution was washed with brine
  2. customdried
  3. concentrationconcentrated
  4. custompurified by silica gel column chromatography (eluted with petroleum ether:EtOAc 10:1 to 1:4))

Sources & evidence

ORD record
ord-620faa5ba7d8450bb4339221b3c97eff
Source dataset
uspto-grants-2015_12
Patent number
US09212168B2

Reaction notes

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