Hydrochloric Acid → (2S,4R)-4-amino-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-pentanoic acid 2-dimethylamino-ethyl ester

HRID 523395Notes

Reaction equation

HRID 523395 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]([OH:13])=[O:12])=[CH:3][CH:2]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NC[CH2:47][CH2:48][N:49]([CH3:51])[CH3:50].CN(CCO)C.CC#N.Cl.O1CCOCC1>C(Cl)Cl>[CH3:51][N:49]([CH3:50])[CH2:48][CH2:47][O:13][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

9

Reactant 7

HCID 313Hydrochloric AcidHCID 6342AcetonitrileHCID 79022-(Dimethylamino)ethanolHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 312751,4-DioxaneHCID 757711-HydroxybenzotriazoleHCID 68181022(2S,4R)-5-Biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxymethyl-2-methyl-pentanoic acid

Product 1

HCID 68181237(2S,4R)-4-amino-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-pentanoic acid 2-dimethylamino-ethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(2S,4R)-5-Biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxymethyl-2-methyl-pentanoic acid (125 mg, 302 μmol), HOBt (240 mg, 1.8 mmol), and EDCI (320 μL, 1.8 mmol) were dissolved in DCM and stirred for 2 minutes. N,N-Dimethylaminoethanol (304 μL, 3.0 mmol) was added and the resulting mixture was stirred at room temperature for 3 hours. The mixture was diluted with DCM and washed with saturated aqueous NaHCO3 solution. The organic layer was separated, dried, concentrated, then purified (Interchim reverse phase chromatography column; 5-70% MeCN in water with 0.5% TFA). The purified material was combined with MeCN (3.0 mL, 58 mmol) and 4 M HCl in dioxane (0.3 mL, 1.2 mmol) and the resulting mixture was stirred at room temperature for 30 minutes. The solvent was removed and azeotroped with toluene (2×) to yield (2S,4R)-4-amino-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-pentanoic acid 2-dimethylamino-ethyl ester.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 3 hours
  2. washwashed with saturated aqueous NaHCO3 solution
  3. customThe organic layer was separated
  4. customdried
  5. concentrationconcentrated
  6. custompurified (Interchim reverse phase chromatography column; 5-70% MeCN in water with 0.5% TFA)
  7. stirringthe resulting mixture was stirred at room temperature for 30 minutes
  8. customThe solvent was removed
  9. customazeotroped with toluene (2×)

Sources & evidence

ORD record
ord-ef9ccd0cc1984c84a54f98ab8d0916d0
Source dataset
uspto-grants-2016_05
Patent number
US09334245B2

Reaction notes

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