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

HRID 1670172Notes

Reaction equation

HRID 1670172 reaction equation
CCN=C=NCCCN(C)C.Cl.Cl.[CH3:14][O:15][C:16](=[O:24])[C@@H:17]([NH2:23])[C@H:18]([N:20]=[N+:21]=[N-:22])[CH3:19].C1C=CC2N(O)N=NC=2C=1.[CH2:35]([C:37]1[CH:42]=[CH:41][C:40]([C:43]2[CH:48]=[CH:47][C:46]([C:49](O)=[O:50])=[CH:45][CH:44]=2)=[CH:39][CH:38]=1)[CH3:36].CCN(C(C)C)C(C)C>C(Cl)Cl.CCCCCC.CCOC(C)=O>[CH3:14][O:15][C:16](=[O:24])[C@@H:17]([NH:23][C:49]([C:46]1[CH:45]=[CH:44][C:43]([C:40]2[CH:41]=[CH:42][C:37]([CH2:35][CH3:36])=[CH:38][CH:39]=2)=[CH:48][CH:47]=1)=[O:50])[C@H:18]([N:20]=[N+:21]=[N-:22])[CH3:19]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 5218014-(4-Ethylphenyl)benzoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86643747(2S,3R)-2-amino-3-azido-butyric acid methylester hydrochloride

Product 1

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

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

A EDC-HCl (249 mg, 1.3 mmol) was added to a stirred colorless solution of azido-Thr-OMe-HCl (4) (195 mg, 11.0 mmol), HOBT (158 mg, 11.0 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-892614c7f4bd4f8c8dd4b759789b0ea7
Source dataset
uspto-grants-2011_08
Patent number
US07989660B2

Reaction notes

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