Hydrochloric Acid → HCID 68181273, compound

HRID 448635Notes

Reaction equation

HRID 448635 reaction equation
[C:1]1([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@@H:8]([NH:17]C(OC(C)(C)C)=O)[CH2:9][C@:10]([CH2:15][OH:16])([CH3:14])[C:11](O)=[O:12])=[CH:3][CH:2]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[OH:52][CH2:53][CH2:54][N:55]1[CH2:59][CH2:58][CH2:57][C:56]1=[O:60].CN1CCOCC1.CC#N.Cl>C(Cl)Cl.O1CCOCC1>[O:60]=[C:56]1[CH2:57][CH2:58][CH2:59][N:55]1[CH2:54][CH2:53][O:52][C:11](=[O:12])[C@@:10]([CH2:15][OH:16])([CH3:14])[CH2:9][C@H:8]([NH2:17])[CH2:7][C:4]1[CH:5]=[CH:6][C:1]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:2][CH:3]=1

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 6342AcetonitrileHCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 769801-(2-Hydroxyethyl)-2-pyrrolidinoneHCID 68181022(2S,4R)-5-Biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxymethyl-2-methyl-pentanoic acid

Product 1

HCID 68181273HCID 68181273, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

(2S,4R)-5-Biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxymethyl-2-methyl-pentanoic acid (100 mg, 242 μmol), HOBt (98 mg, 726 μmol), and EDCI (128 μL, 726 μmol) were dissolved in DCM (2 mL). After stirring for 15 minutes, 1-(2-hydroxyethyl)-2-pyrrolidone (218 μL, 1.9 mmol) and 4-methylmorpholine (106 μL, 967 μmol) were added. The resulting mixture was stirred at room temperature overnight, and then the reaction was quenched with water. The DCM layer was separated, concentrated, purified ((Interchim reverse phase chromatography column), and dried under vacuum. The purified material was combined with MeCN (1 mL, 20 mmol) and 4 M HCl in dioxane (240 μL, 970 μmmol) and stirred at room temperature for 1 hour. The solvent was then removed to yield (2S,4R)-4-amino-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-pentanoic acid 2-(2-oxo-pyrrolidin-1-yl)-ethyl ester.

Workup

  1. stirringThe resulting mixture was stirred at room temperature overnight
  2. customthe reaction was quenched with water
  3. customThe DCM layer was separated
  4. concentrationconcentrated
  5. custompurified ((Interchim reverse phase chromatography column)
  6. customdried under vacuum
  7. stirringstirred at room temperature for 1 hour
  8. customThe solvent was then removed

Sources & evidence

ORD record
ord-72130b56b5ad479499eb8e003d9c4cc0
Source dataset
uspto-grants-2013_07
Patent number
US08481044B2

Reaction notes

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