1-Hydroxybenzotriazole → 3-(R)-Azido-2-(S)-[(4'-ethyl-biphenyl-4-carbonyl)-amino]-butyric acid methyl ester

HRID 900548Notes

Reaction equation

HRID 900548 reaction equation
CC[N:3]=C=NCCCN(C)C.Cl.C1C=[CH:15][C:16]2[N:21](O)[N:20]=[N:19]C=2C=1.[CH2:23]([C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:36]=[CH:35][C:34]([C:37]([OH:39])=O)=[CH:33][CH:32]=2)=[CH:27][CH:26]=1)[CH3:24].CCN(C(C)C)C(C)C.CCCCCC.C[CH2:56][O:57][C:58]([CH3:60])=[O:59]>C(Cl)Cl>[CH3:56][O:57][C:58](=[O:59])[C@@H:60]([NH:3][C:37]([C:34]1[CH:33]=[CH:32][C:31]([C:28]2[CH:27]=[CH:26][C:25]([CH2:23][CH3:24])=[CH:30][CH:29]=2)=[CH:36][CH:35]=1)=[O:39])[C@H:16]([N:21]=[N+:20]=[N-:19])[CH3:15]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 5218014'-ethyl-4-biphenylcarboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21226206Ethyl acetate hexane

Product 1

HCID 596972273-(R)-Azido-2-(S)-[(4'-ethyl-biphenyl-4-carbonyl)-amino]-butyric acid methyl esterYield 67%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A EDC.HCl (249 mg, 1.3 mmol) was added to a stirred colorless solution of azido-Thr-OMe.HCl (4) (195 mg, 1.0 mmol), HOBT (158 mg, 1.0 mmol), 4′-Ethyl-biphenyl-4-carboxylic acid (5) (226 mg, 1.0 mmol) and DIEA (0.44 ml, 2.5 mmol) in DCM (10 ml) at rt under N2. After 24 h, the reaction had reached completion by TLC (Hexane/EtOAc (60:40) (Rf=0.3)) and LCMS. The reaction was evaporated under reduced pressure to a brown tar. The crude product was dissolved in EtOAc (100 ml) and washed with 0.2N aq. HCl (2×50 ml), aq. sat. NaHCO3 (50 ml), brine (50 ml), dried (Na2SO4), filtered and concentrated under reduced pressure to yield a crude brown solid. The crude material was further purified by column chromatography eluting with Hexane/EtOAc (70:30) giving 245 mg (67% yield) of pure product after evaporation and drying in vacuo.

Workup

  1. customThe reaction was evaporated under reduced pressure to a brown tar
  2. dissolutionThe crude product was dissolved in EtOAc (100 ml)
  3. washwashed with 0.2N aq. HCl (2×50 ml), aq. sat. NaHCO3 (50 ml), brine (50 ml)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto yield a crude brown solid
  8. customThe crude material was further purified by column chromatography
  9. washeluting with Hexane/EtOAc (70:30)

Sources & evidence

ORD record
ord-34dc51a37d29403e980404e239f71541
Source dataset
uspto-grants-2008_04
Patent number
US07358359B2

Reaction notes

Loading…