Diisopropylethylamine → (S)-2-[(S)-3-(4-But-3-enyloxy-phenyl)-2-tert-butoxycarbonylamino-propionylamino]-4-ethyl-pentanoic acid methyl ester

HRID 2371311Notes

Reaction equation

HRID 2371311 reaction equation
[CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C@H:13]([NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:14]([OH:16])=O)=[CH:8][CH:7]=1)[CH2:2][CH:3]=[CH2:4].[CH3:25]N(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[CH3:50][O:51][C:52](=[O:59])[C@H:53]([CH2:55][CH:56]([CH3:58])[CH3:57])[NH2:54].CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[CH3:50][O:51][C:52](=[O:59])[C@@H:53]([NH:54][C:14](=[O:16])[C@@H:13]([NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:12][C:9]1[CH:8]=[CH:7][C:6]([O:5][CH2:1][CH2:2][CH:3]=[CH2:4])=[CH:11][CH:10]=1)[CH2:55][CH:56]([CH2:58][CH3:25])[CH3:57]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2723695Leucine methyl ester hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66847114(S)-3-(4-But-3-enyloxy-phenyl)-2-tert-butoxycarbonylamino-propionic acid

Product 1

HCID 66847191(S)-2-[(S)-3-(4-But-3-enyloxy-phenyl)-2-tert-butoxycarbonylamino-propionylamino]-4-ethyl-pentanoic acid methyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Carboxylic acid 19 (2.60 g, 7.75 mmol), HATU (3.24 g, 8.53 mmol) and leucine methyl ester hydrochloride (2.82 g, 15.5 mmol) were dissolved in DMF (40 mL). DIPEA was added (5.40 mL, 31.0 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. The crude material was purified by flash chromatography on silica using a gradient of EtOAc and (50/70) petroleum ether to yield a white solid, 2.30 g, 64%. Rf=0.34 (1/2 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. customThe crude material was purified by flash chromatography on silica using a gradient of EtOAc and (50/70) petroleum ether
  7. customto yield a white solid, 2.30 g, 64%

Sources & evidence

ORD record
ord-5711ebfc006e48aeb2954d86da829005
Source dataset
uspto-grants-2014_04
Patent number
US08710178B2

Reaction notes

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