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

HRID 2371303Notes

Reaction equation

HRID 2371303 reaction equation
[CH2:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C@H:12]([NH:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C:13]([NH:15][C@@H:16]([CH2:20][CH:21]([CH3:23])[CH3:22])[C:17]([OH:19])=O)=[O:14])=[CH:7][CH:6]=1)[CH:2]=[CH2:3].CN(C(ON1N=N[C:42]2[CH:43]=CC=N[C:41]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CC[N:58](C(C)C)C(C)C.C[CH2:66][O:67][C:68]([CH3:70])=[O:69]>CN(C=O)C>[CH3:66][O:67][C:68](=[O:69])[C@@H:70]([NH:58][C:17](=[O:19])[C@@H:16]([NH:15][C:13](=[O:14])[C@@H:12]([NH:24][C:25]([O:27][C:28]([CH3:30])([CH3:29])[CH3:31])=[O:26])[CH2:11][C:8]1[CH:9]=[CH:10][C:5]([O:4][CH2:1][CH:2]=[CH2:3])=[CH:6][CH:7]=1)[CH2:20][CH:21]([CH3:22])[CH3:23])[CH2:43][CH:42]=[CH2:41]

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 66847292(S)-2-[(S)-3-(4-Allyloxy-phenyl)-2-tert-butoxycarbonylamino-propionylamino]-4-methyl-pentanoic acid

Product 1

HCID 66847360(S)-2-{(S)-2-[(S)-3-(4-Allyloxy-phenyl)-2-tert-butoxycarbonylamino-propionylamino]-4-methyl-pentanoylamino}-pent-4-enoic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Carboxylic acid 2 (2.86 g, 6.58 mmol), HATU (2.75 g, 7.24 mmol) and (S)-allyl-glycine methyl ester hydrochloride (1.20 g, 7.24 mmol) were dissolved in DMF (30 mL). DIPEA was added (4.60 mL, 26.4 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 1/3 EtOAc/(50/70) petroleum ether to 2/1 EtOAc/(50/70) petroleum ether to yield a white solid, 1.40 g, 39%. Rf=0.70 (1/1 EtOAc/(50/70) petroleum ether).

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 1/3 EtOAc/(50/70) petroleum ether to 2/1 EtOAc/(50/70) petroleum ether
  8. customto yield a white solid, 1.40 g, 39%

Sources & evidence

ORD record
ord-256c54ad823d446aa69232033e853f8b
Source dataset
uspto-grants-2014_04
Patent number
US08710178B2

Reaction notes

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