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

HRID 1377152Notes

Reaction equation

HRID 1377152 reaction equation
[Li+].[OH-].[C:3]([NH:10][C@H:11]([C@H:19]1[O:23][C:22](=[O:24])[C@H:21]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[CH2:20]1)[CH2:12][CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].[NH4+].[Cl-].C(O)(=O)CC(CC(O)=O)(C(O)=O)[OH:39]>COCCOC.CCOCC>[C:3]([NH:10][C@@H:11]([CH2:12][CH:13]1[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]1)[C@@H:19]([OH:39])[CH2:20][C@@H:21]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=1)[C:22]([OH:23])=[O:24])([O:5][C:6]([CH3:9])([CH3:7])[CH3:8])=[O:4]

Participants

7

Reactant 4

HCID 311Citric AcidHCID 3939Lithium HydroxideHCID 25517Ammonium ChlorideHCID 157083255(S)-[1(S)-(Boc-Amino)-2-cyclohexylethyl]-3(R)-[(p-methoxyphenyl)methyl]dihydrofuran-2-(3H)-one

Product 1

HCID 228763985(S)-(Boc-Amino)-4(S)-hydroxy-6-cyclohexyl-2(R)-[(p-methoxyphenyl)methyl]hexanoic acid

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

1000 ml of 1M aqueous LiOH solution are added, under a protective gas, to a solution of 103 g (239 mmol) of 5(S)-[1(S)-(Boc-amino)-2-cyclohexylethyl]-3(R)-[(p-methoxyphenyl)methyl]dihydrofuran-2-(3H)-one in 800 ml 1,2-dimethoxyethane. After 3 h at RT, the reaction solution is poured onto an ice-cold mixture of 1.5 l of sat. NH4Cl solution, 1 l of 10% citric acid solution and 2 l of ether. The aqueous phase is separated off and extracted 2× with 1 l of ether on each occasion. The organic phases are washed 4× with ice-water and finally with saline. Drying with sodium sulfate and evaporating yields the title compound from the organic phases: tRet (II)=16.0 min; FAB-MS (M+H)+ =450.

Workup

  1. customThe aqueous phase is separated off
  2. extractionextracted 2× with 1 l of ether on each occasion
  3. washThe organic phases are washed 4× with ice-water
  4. dry with materialDrying with sodium sulfate
  5. customevaporating

Sources & evidence

ORD record
ord-aa68f12b44a441ed85534044472f0ccd
Source dataset
uspto-grants-1997_09
Patent number
US05663200

Reaction notes

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