Citric Acid → 5(S)-(Boc-amino)-4(S)-hydroxy-6-cyclohexyl-2(R)-(4-benzyloxy-benzyl)-hexanoic acid

HRID 1377157Notes

Reaction equation

HRID 1377157 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C@@H:16]2[CH2:20][C@@H:19]([C@@H:21]([NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:22][CH:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)[O:18][C:17]2=[O:37])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Li+].[NH4+].[Cl-].C(O)(=O)CC(CC(O)=O)(C(O)=O)[OH:45]>C(COC)OC.CO.C(Cl)Cl>[C:30]([NH:29][C@@H:21]([CH2:22][CH:23]1[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]1)[C@@H:19]([OH:45])[CH2:20][C@@H:16]([CH2:15][C:12]1[CH:11]=[CH:10][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:14][CH:13]=1)[C:17]([OH:18])=[O:37])([O:32][C:33]([CH3:35])([CH3:36])[CH3:34])=[O:31]

Participants

8

Reactant 4

HCID 311Citric AcidHCID 3939Lithium HydroxideHCID 25517Ammonium ChlorideHCID 566153103(R)-[(4-Benzyloxyphenyl)methyl]-5(S)-[1(S)-(Boc-amino)-2-cyclohexylethyl]dihydrofuran-2-one

Product 1

HCID 228742765(S)-(Boc-amino)-4(S)-hydroxy-6-cyclohexyl-2(R)-(4-benzyloxy-benzyl)-hexanoic acid

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

2.4 g (4.728 mmol) of 3(R)-[(4-benzyloxyphenyl)methyl]-5(S)-[1(S)-(Boc-amino)-2-cyclohexylethyl]dihydrofuran-2-one in 10 ml of dimethoxyethane are hydrolysed, under a protective gas, with 9.45 ml of a 1M solution of lithium hydroxide. After 17 h at RT, the reaction mixture is treated with an ice-cold mixture of 324 ml of sat. NH4Cl solution, 27 ml of 10% citric acid solution and 134 ml of methylene chloride. Methanol is added in order to dissolve the product completely. The aqueous phase is separated off and extracted 2× with methylene chloride. The organic phases are washed with saline, dried with Na2SO4 and evaporated. The crude product is purified by column chromatography (SiO2, eluent C), with the title compound being obtained. TLC Rf (C)=0.35; tRet (II)=17.88 min. FAB-MS (M+H+)=526.

Workup

  1. dissolutionto dissolve the product completely
  2. customThe aqueous phase is separated off
  3. extractionextracted 2× with methylene chloride
  4. washThe organic phases are washed with saline
  5. dry with materialdried with Na2SO4
  6. customevaporated
  7. customThe crude product is purified by column chromatography (SiO2, eluent C), with the title compound
  8. custombeing obtained

Sources & evidence

ORD record
ord-3f136c87d1624db29fc2e11df23dbc39
Source dataset
uspto-grants-1997_09
Patent number
US05663200

Reaction notes

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