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

HRID 535200Notes

Reaction equation

HRID 535200 reaction equation
Cl[CH2:2][O:3][C:4](=[O:14])[C@@H:5]([NH:9][C:10]([O:12][CH3:13])=[O:11])[CH:6]([CH3:8])[CH3:7].[C:15]1([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH:20]=[CH:19][C:18]([CH2:21][C@@H:22]([NH:31]C(OC(C)(C)C)=O)[CH2:23][C@:24]([CH2:29][OH:30])([CH3:28])[C:25]([OH:27])=[O:26])=[CH:17][CH:16]=1.CCN(CC)CC.Cl.O1CCOCC1>CC(C)=O.CC#N>[CH3:13][O:12][C:10]([NH:9][C@@H:5]([CH:6]([CH3:8])[CH3:7])[C:4]([O:3][CH2:2][O:27][C:25](=[O:26])[C@@:24]([CH2:29][OH:30])([CH3:28])[CH2:23][C@H:22]([NH2:31])[CH2:21][C:18]1[CH:19]=[CH:20][C:15]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)=[CH:16][CH:17]=1)=[O:14])=[O:11]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 68181022(2S,4R)-5-Biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxymethyl-2-methyl-pentanoic acidHCID 86669865(S)-chloromethyl 2-((methoxycarbonyl)amino)-3-methylbutanoate

Product 1

HCID 86669864(2S,4R)-4-amino-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-pentanoic acid (S)-2-methoxycarbonylamino-3-methyl-butyryloxymethyl ester

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 6342AcetonitrileSolvent

Procedure

(S)-2-Methoxycarbonylamino-3-methyl-butyric acid chloromethyl ester (140 mg, 630 μmol) was added to a mixture of (2S,4R)-5-biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxymethyl-2-methyl-pentanoic acid (0.2 g, 484 μmol) and Et3N (71 μL, 508 μmol) in acetone (10 mL). The mixture was refluxed for 24 hours and the reaction monitored for completion. When the reaction was complete, the product was purified (Interchim reverse phase chromatography column) the solvent was removed under vacuum. MeCN (2 mL) and 4 M HCl in 1,4-dioxane (2 mL, 8 mmol) was added and the resulting mixture was stirred for 30 minutes. The solvent was evaporated under vacuum and the product was azeotroped with toluene (1×) to yield (2S,4R)-4-amino-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-pentanoic acid (S)-2-methoxycarbonylamino-3-methyl-butyryloxymethyl ester.

Workup

  1. temperatureThe mixture was refluxed for 24 hours
  2. customthe product was purified (Interchim reverse phase chromatography column) the solvent
  3. customwas removed under vacuum
  4. customThe solvent was evaporated under vacuum
  5. customthe product was azeotroped with toluene (1×)

Sources & evidence

ORD record
ord-53e33f6285c84049b8d24eb583ff3f7e
Source dataset
uspto-grants-2014_10
Patent number
US08853427B2

Reaction notes

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