Lithium Hydroxide → 5(S)-(Boc-Amino)-4(S)-hydroxy-6-phenyl-2(R)-[(2,4-dimethoxyphenyl)methyl]hexanoic acid

HRID 1377181Notes

Reaction equation

HRID 1377181 reaction equation
[C:1]([NH:8][C@H:9]([C@H:17]1[O:21][C:20](=[O:22])[C@H:19]([CH2:23][C:24]2[CH:29]=CC(OC)=[CH:26][C:25]=2[O:32][CH3:33])[CH2:18]1)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[Li+].[OH-:35].CO[CH2:38][CH2:39][O:40][CH3:41]>O.C(OCC)(=O)C>[C:1]([NH:8][C@@H:9]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C@@H:17]([OH:35])[CH2:18][C@@H:19]([CH2:23][C:24]1[CH:29]=[CH:38][C:39]([O:40][CH3:41])=[CH:26][C:25]=1[O:32][CH3:33])[C:20]([OH:21])=[O:22])([O:3][C:4]([CH3:7])([CH3:5])[CH3:6])=[O:2]

Participants

6

Reactant 3

HCID 3939Lithium HydroxideHCID 80711,2-DimethoxyethaneHCID 701496735(S)-[1(S)-(Boc-Amino)-2-phenylethyl]-3(R)-[(2,4-dimethoxyphenyl)methyl]-dihydrofuran-2-(3H)-one

Product 1

HCID 228764045(S)-(Boc-Amino)-4(S)-hydroxy-6-phenyl-2(R)-[(2,4-dimethoxyphenyl)methyl]hexanoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1.58 g (3.47 mmol) of 5(S)-[1(S)-(Boc-amino)-2-phenylethyl]-3(R)-[(2,4-dimethoxyphenyl)methyl]dihydrofuran-2-(3H)-one in 56 ml of ethylene glycol dimethyl ether and 28.2 ml of water is treated, at RT, with 13.87 ml of a 1M solution of LiOH in water, and this mixture is stirred for 1.75 h. After that, the reaction mixture is diluted with ethyl acetate and a little THF and the whole is washed firstly with a mixture consisting of 170.6 ml of sat. ammonium chloride solution and 14.25 ml of 10% citric acid solution (both being cold) and then with saline. The combined aqueous phases are reextracted with ethyl acetate. The combined organic phases are dried over Na2SO4 and evaporated on a RE at about 30° C. The residue, which is the title compound, is triturated with hexane and filtered off with suction. M.p.: 144°-145° C. TLC Rf (D)=at the start. FAB-MS (M+H)+ =474. HPLC TRet =14.34 min (gradient II). IR(KBr)=u.a. 3420, 3350, 2818, 1686, 1518 and 1508 cm-1. 1H-NMR(CD3OD)=inter alia 7.30-7.09/m (5H); 6.94/d (1H); 6.47/d (1H); 6.37/dxd (1H); 3,78 and 3.75/each s (each 3H); 1.33/s (9H).

Workup

  1. washa little THF and the whole is washed firstly with a mixture
  2. dry with materialThe combined organic phases are dried over Na2SO4
  3. customevaporated on a RE at about 30° C
  4. customis triturated with hexane
  5. filtrationfiltered off with suction
  6. customHPLC TRet =14.34 min (gradient II)

Sources & evidence

ORD record
ord-925f4c9625a746cfbb2514373318a8cf
Source dataset
uspto-grants-1997_09
Patent number
US05663200

Reaction notes

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