Hydrochloric Acid → (2S,4R)-4-amino-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-pentanoic acid oxetan-3-yl ester

HRID 535180Notes

Reaction equation

HRID 535180 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=NCCCN(C)C.[O:52]1[CH2:55][CH:54](O)[CH2:53]1.CN1CCOCC1.CC#N.Cl.O1CCOCC1>C(Cl)Cl>[O:52]1[CH2:55][CH:54]([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]2[CH:5]=[CH:6][C:1]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[CH:2][CH:3]=2)[CH2:53]1

Participants

10

Reactant 8

HCID 313Hydrochloric AcidHCID 6342AcetonitrileHCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 312751,4-DioxaneHCID 757711-HydroxybenzotriazoleHCID 9942117Oxetan-3-olHCID 68181022(2S,4R)-5-Biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxymethyl-2-methyl-pentanoic acid

Product 1

HCID 68181152(2S,4R)-4-amino-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-pentanoic acid oxetan-3-yl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(2S,4R)-5-Biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxymethyl-2-methyl-pentanoic acid (100 mg, 242 μmol), HOBt (98 mg, 720 μmol), and EDCI (130 μL, 720 μmol) were dissolved in DCM and stirred for 15 minutes. Oxetan-3-ol (140 mg, 1.9 mmol) and 4-methylmorpholine (110 μL, 970 μmol) were added and the resulting mixture was stirred at room temperature for 2 hours. The reaction was quenched with water and the DCM layer was separated and concentrated. The product was then 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 μmol) and the resulting mixture was stirred at room temperature for 1 hour. The solvent was removed to yield (2S,4R)-4-amino-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-pentanoic acid oxetan-3-yl ester.

Workup

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

Sources & evidence

ORD record
ord-ac97890a8a8747eb8bc5149c5de80f55
Source dataset
uspto-grants-2014_10
Patent number
US08853427B2

Reaction notes

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