Citric Acid → 5(S)-(Boc-Amino)-4(S)-hydroxy-6-[p-(2-methoxyethoxy)phenyl]-2(R)-[(p-benzyloxyphenyl)methyl]hexanoic acid

HRID 1585368Notes

Reaction equation

HRID 1585368 reaction equation
[C:1]([NH:8][C@H:9]([C@H:22]1[O:26][C:25](=[O:27])[C@H:24]([CH2:28][C:29]2[CH:34]=[CH:33][C:32]([O:35][CH2:36][C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)=[CH:31][CH:30]=2)[CH2:23]1)[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][O:20][CH3:21])=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[OH-].[Li+].[NH4+].[Cl-].C(O)(=O)CC(CC(O)=O)(C(O)=O)[OH:50]>C(COC)OC.O.CO.C(Cl)Cl>[C:1]([NH:8][C@@H:9]([CH2:10][C:11]1[CH:12]=[CH:13][C:14]([O:17][CH2:18][CH2:19][O:20][CH3:21])=[CH:15][CH:16]=1)[C@@H:22]([OH:50])[CH2:23][C@@H:24]([CH2:28][C:29]1[CH:34]=[CH:33][C:32]([O:35][CH2:36][C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)=[CH:31][CH:30]=1)[C:25]([OH:26])=[O:27])([O:3][C:4]([CH3:6])([CH3:7])[CH3:5])=[O:2]

Participants

9

Reactant 4

HCID 311Citric AcidHCID 3939Lithium HydroxideHCID 25517Ammonium ChlorideHCID 701494025(S)-[1(S)-(Boc-Amino)-2-[p-(2-methoxyethoxy)phenyl]ethyl]-3(R)-[(p-benzyloxyphenyl)methyl]dihydrofuran-2-(3H)-one

Product 1

HCID 228763995(S)-(Boc-Amino)-4(S)-hydroxy-6-[p-(2-methoxyethoxy)phenyl]-2(R)-[(p-benzyloxyphenyl)methyl]hexanoic acid

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

3.85 g (6.68 mmol) of 5(S)-[1(S)-(Boc-amino)-2-[p-(2-methoxyethoxy)phenyl]ethyl]-3(R)-[(p-benzyloxyphenyl)methyl]dihydrofuran-2-(3H)-one in 107 ml of dimethoxyethane and 54 ml of water are hydrolysed, under a protective gas, with 26.5 ml of a 1 M lithium hydroxide solution. 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: tRet (I)=15.8 min; FAB-MS (M+H)+ =594.

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. customtRet (I)=15.8 min

Sources & evidence

ORD record
ord-bfba52a638f84ee9b8ab44085182616f
Source dataset
uspto-grants-1999_08
Patent number
US05935976

Reaction notes

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