Ethyl Acetate → (2S,4R)-tert-butyl 2-((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropylcarbamoyl)-4-hydroxypyrrolidine-1-carboxylate

HRID 403421

Reaction equation

HRID 403421 reaction equation
[C:1]([N:8]1[CH2:16][C@H:14]([OH:15])[CH2:13][C@H:9]1[C:10]([OH:12])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN(C(ON1N=N[C:27]2[CH:28]=[CH:29][CH:30]=[N:31][C:26]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.S(C1C=CC(C)=CC=1)([O-])(=O)=O.C([NH2+]C1CC1)=C.[CH3:67][CH2:68][O:69][C:70](C)=[O:71]>>[CH2:68]([O:69][C:70]([C@@:30]1([NH:31][C:10]([C@@H:9]2[CH2:13][C@@H:14]([OH:15])[CH2:16][N:8]2[C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])=[O:12])[CH2:29][C@H:28]1[CH:27]=[CH2:26])=[O:71])[CH3:67]

Participants

6

Reactant 5

HCID 8857Ethyl Acetate2×HCID 81531Diisopropylethylamine2×HCID 88804(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86664338Vinylcyclopropylammonium tosylate

Product 1

HCID 57892908(2S,4R)-tert-butyl 2-((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropylcarbamoyl)-4-hydroxypyrrolidine-1-carboxylateYield 85%

Procedure

To a stiffing slurry of N-Boc-hydroxy proline (78 g), HATU (128 g), and EtOAc (558 g), at 0° C., was added diisopropylethylamine (65 g). After 45 min, a solution containing vinylcyclopropylammonium tosylate (100 g), diisopropylethylamine (65.0 g), and EtOAc (366 g) was added to the activated ester solution. After 3 h at 10° C., the reaction slurry was filtered and the resulting cake was rinsed with EtOAc (2 L). The resulting filtrate was washed with a 10% aqueous solution of NaCl (5×770 g). The product-containing organic layer was filtered, concentrated under reduced pressure to an oil (85% yield).

Workup

  1. waitAfter 3 h at 10° C.
  2. filtrationthe reaction slurry was filtered
  3. washthe resulting cake was rinsed with EtOAc (2 L)
  4. washThe resulting filtrate was washed with a 10% aqueous solution of NaCl (5×770 g)
  5. filtrationThe product-containing organic layer was filtered

Sources & evidence

ORD record
ord-4928ddd2718149ada645de70ac1b9b72
Source dataset
uspto-grants-2014_06
Patent number
US08748374B2

Linked notes

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