Hydrochloric Acid → (2S,4R)-4-amino-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-pentanoic acid 1-cyclohexyloxycarbonyloxy-ethyl ester

HRID 535201Notes

Reaction equation

HRID 535201 reaction equation
[C:1](=[O:13])([O:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)[O:2][CH:3](Cl)[CH3:4].[C:14]1([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH:19]=[CH:18][C:17]([CH2:20][C@@H:21]([NH:30]C(OC(C)(C)C)=O)[CH2:22][C@:23]([CH2:28][OH:29])([CH3:27])[C:24]([OH:26])=[O:25])=[CH:16][CH:15]=1.CCN(CC)CC.Cl.O1CCOCC1>CC(C)=O.CC#N>[CH:7]1([O:6][C:1]([O:2][CH:3]([O:26][C:24](=[O:25])[C@@:23]([CH2:28][OH:29])([CH3:27])[CH2:22][C@H:21]([NH2:30])[CH2:20][C:17]2[CH:18]=[CH:19][C:14]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)=[CH:15][CH:16]=2)[CH3:4])=[O:13])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 112295291-Chloroethyl Cyclohexyl CarbonateHCID 68181022(2S,4R)-5-Biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxymethyl-2-methyl-pentanoic acid

Product 1

HCID 68181297(2S,4R)-4-amino-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-pentanoic acid 1-cyclohexyloxycarbonyloxy-ethyl ester

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 6342AcetonitrileSolvent

Procedure

1-Chloroethyl cyclohexyl carbonate (240 mg, 1.2 mmol) was added to a mixture of (2S,4R)-5-biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxymethyl-2-methyl-pentanoic acid (300 mg, 726 μmol) and Et3N (106 μL, 762 μmol) in acetone (10 mL). The mixture was refluxed for 24 hours and the reaction monitored for completion. The individual isomers were separated (˜1:1) and purified (Interchim reverse phase chromatography column) the solvent was removed under vacuum. MeCN (2 mL) and 4 M HCl in 1,4-dioxane (3 mL, 10 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 1-cyclohexyloxycarbonyloxy-ethyl ester.

Workup

  1. temperatureThe mixture was refluxed for 24 hours
  2. customThe individual isomers were separated (˜1:1)
  3. custompurified (Interchim reverse phase chromatography column) the solvent
  4. customwas removed under vacuum
  5. customThe solvent was evaporated under vacuum
  6. customthe product was azeotroped with toluene (1×)

Sources & evidence

ORD record
ord-cc283e7fad394d6f9f9dacba22e802f1
Source dataset
uspto-grants-2014_10
Patent number
US08853427B2

Reaction notes

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