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

HRID 448644Notes

Reaction equation

HRID 448644 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-408832e6487f40b8ad3a0e4872f6cecf
Source dataset
uspto-grants-2013_07
Patent number
US08481044B2

Reaction notes

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