1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Di-tert-butyl N-(3-(2-(5-(tert-butoxycarbonyl)-5-(2-tert-butoxy-2-oxoethyl)-4,5-dihydro-1,2-oxazol-3-yl)-4-hydroxyphenyl)propanoyl)-L-aspartate

HRID 1486893Notes

Reaction equation

HRID 1486893 reaction equation
[C:1]([O:5][C:6]([C:8]1([CH2:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[O:12][N:11]=[C:10]([C:13]2[CH:18]=[C:17]([OH:19])[CH:16]=[CH:15][C:14]=2[CH2:20][CH2:21][C:22](O)=[O:23])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:34][C@H:35]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>O.CN(C=O)C.C(N(CC)CC)C>[C:1]([O:5][C:6]([C:8]1([CH2:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[O:12][N:11]=[C:10]([C:13]2[CH:18]=[C:17]([OH:19])[CH:16]=[CH:15][C:14]=2[CH2:20][CH2:21][C:22]([NH:34][C@H:35]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:36][C:37]([O:39][C:40]([CH3:42])([CH3:43])[CH3:41])=[O:38])=[O:23])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 13768146L-Aspartic acid, bis(1,1-dimethylethyl) ester, hydrochlorideHCID 1182928123-(2-(5-(tert-Butoxycarbonyl)-5-(2-tert-butoxy-2-oxoethyl)-4,5-dihydro-1,2-oxazol-3-yl)-4-hydroxyphenyl)propanoic acid

Product 1

HCID 118292852Di-tert-butyl N-(3-(2-(5-(tert-butoxycarbonyl)-5-(2-tert-butoxy-2-oxoethyl)-4,5-dihydro-1,2-oxazol-3-yl)-4-hydroxyphenyl)propanoyl)-L-aspartateYield 47.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

A mixture of 3-(2-(5-(tert-butoxycarbonyl)-5-(2-tert-butoxy-2-oxoethyl)-4,5-dihydro-1,2-oxazol-3-yl)-4-hydroxyphenyl)propanoic acid (214 mg), di-tert-butyl L-aspartate hydrochloride (161 mg), WSC (89 mg), HOBt (77 mg), triethylamine (0.080 mL), and DMF (2 mL) was stirred at room temperature for 3 days. To the reaction mixture, water was added, followed by extraction with ethyl acetate. The extract was washed with brine and dried over anhydrous magnesium sulfate, and then, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (154 mg).

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe extract was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. distillationthe solvent was distilled off under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-488a6733d0c048b89b5d73aff674a861
Source dataset
uspto-grants-2016_08
Patent number
US09428470B2

Reaction notes

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