Hydrochloric Acid → HCID 86669863, compound

HRID 535198Notes

Reaction equation

HRID 535198 reaction equation
Cl[CH2:2][O:3][C:4](=[O:20])[C@@H:5]([NH:9][C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])[CH:6]([CH3:8])[CH3:7].[C:21]1([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[CH:26]=[CH:25][C:24]([CH2:27][C@@H:28]([NH:37]C(OC(C)(C)C)=O)[CH2:29][C@:30]([CH2:35][OH:36])([CH3:34])[C:31]([OH:33])=[O:32])=[CH:23][CH:22]=1.CCN(CC)CC.Cl.O1CCOCC1>CC(C)=O.CC#N>[CH2:13]([O:12][C:10]([NH:9][C@@H:5]([CH:6]([CH3:8])[CH3:7])[C:4]([O:3][CH2:2][O:33][C:31](=[O:32])[C@@:30]([CH2:35][OH:36])([CH3:34])[CH2:29][C@H:28]([NH2:37])[CH2:27][C:24]1[CH:25]=[CH:26][C:21]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)=[CH:22][CH:23]=1)=[O:20])=[O:11])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

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 68181315HCID 68181315, compound

Product 1

HCID 86669863HCID 86669863, compound

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 6342AcetonitrileSolvent

Procedure

(S)-2-Benzyloxycarbonylamino-3-methyl-butyric acid chloromethyl ester (232 mg, 774 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-benzyloxycarbonylamino-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-946097bded5548e198b29691594145bb
Source dataset
uspto-grants-2014_10
Patent number
US08853427B2

Reaction notes

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