Ethyl Acetate → (S)-2-{(S)-2-[(S)-3-(4-Allyloxy-phenyl)-2-tert-butoxycarbonylamino propionylamino]-3-methylbutyrylamino}-pent-4-enoic acid methyl ester

HRID 58377

Reaction equation

HRID 58377 reaction equation
[CH2:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C@H:12]([NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C:13]([NH:15][C@@H:16]([CH:20]([CH3:22])[CH3:21])C(O)=O)=[O:14])=[CH:7][CH:6]=1)[CH:2]=[CH2:3].C[N:32]([C:34]([O:38]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)[CH:58]([CH3:60])[CH3:59].C[CH2:65][O:66][C:67]([CH3:69])=[O:68]>CN(C=O)C>[CH3:65][O:66][C:67](=[O:68])[C@@H:69]([NH:32][C:34](=[O:38])[C@@H:16]([NH:15][C:13](=[O:14])[C@@H:12]([NH:23][C:24]([O:26][C:27]([CH3:28])([CH3:30])[CH3:29])=[O:25])[CH2:11][C:8]1[CH:7]=[CH:6][C:5]([O:4][CH2:1][CH:2]=[CH2:3])=[CH:10][CH:9]=1)[CH:20]([CH3:22])[CH3:21])[CH2:60][CH:58]=[CH2:59]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66847200(S)-2-[(S)-3-(4-Allyloxy-phenyl)-2-tert-butoxycarbonylamino-propionylamino]-3-methyl-butyric acid

Product 1

HCID 66847339(S)-2-{(S)-2-[(S)-3-(4-Allyloxy-phenyl)-2-tert-butoxycarbonylamino propionylamino]-3-methylbutyrylamino}-pent-4-enoic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Carboxylic acid 43 (1.00 g, 2.38 mmol), HATU (2.62 mmol) and (S)-allyl-glycine methyl ester hydrochloride (2.62 mmol) were dissolved in DMF (30 mL). DIPEA was added (9.52 mmol) and the reaction mixture was stirred at rt for 18 h before being partitioned between EtOAc and 1M hydrochloric acid. The organic phase was washed sequentially with 1M hydrochloric acid and brine before being dried (MgSO4), filtered and concentrated in vacuo. Purification was achieved using flash chromatography, eluting with a gradient of EtOAc and (50/70) petroleum ether to yield a white solid, 1.05 g, 83%. Rf=0.48 (1/1 EtOAc/(50/70) petroleum ether). m.p. 106-108° C.

Workup

  1. custombefore being partitioned between EtOAc and 1M hydrochloric acid
  2. washThe organic phase was washed sequentially with 1M hydrochloric acid and brine
  3. dry with materialbefore being dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification
  7. washeluting with a gradient of EtOAc and (50/70) petroleum ether
  8. customto yield a white solid, 1.05 g, 83%

Sources & evidence

ORD record
ord-57570430308e4a12bc8ce5b51ca9d9a9
Source dataset
uspto-grants-2016_09
Patent number
US09434762B2

Linked notes

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