Lithium hydroxide, monohydrate → 3-(5-{(1R)-4-Cyclohexyl-1-[2-(hydroxyamino)-2-oxoethyl]butyl}1,2,4-oxadiazol-3-yl)propanoic acid

HRID 1279797Notes

Reaction equation

HRID 1279797 reaction equation
[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:16]2[O:20][N:19]=[C:18]([CH2:21][CH2:22][C:23]([O:25]CC)=[O:24])[N:17]=2)[CH2:11][C:12]([NH:14][OH:15])=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.O.[OH-].[Li+]>O1CCOCC1.O>[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:16]2[O:20][N:19]=[C:18]([CH2:21][CH2:22][C:23]([OH:25])=[O:24])[N:17]=2)[CH2:11][C:12]([NH:14][OH:15])=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 10156678Ethyl 3-(5-{(1R)-4-cyclohexyl-1-[2-(hydroxyamino)-2-oxoethyl]butyl}-1,2,4-oxadiazol-3-yl)propanoate

Product 1

HCID 102694873-(5-{(1R)-4-Cyclohexyl-1-[2-(hydroxyamino)-2-oxoethyl]butyl}1,2,4-oxadiazol-3-yl)propanoic acidYield 67.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

A solution of ethyl 3-(5-{(1R)-4-cyclohexyl-1 -[2-(hydroxyamino)-2-oxoethyl]butyl}-1,2,4-oxadiazol-3- yl)propanoate (Example 54) (58 mg, 0.15 mmol) in 1,4-dioxan (2 ml) and water (1 ml) was treated with lithium hydroxide monohydrate (13 mg, 0.31 mmol) and stirred at room temperature for 2 hours. The reaction mixture was diluted with water and washed with diethylether (×2). The aqueous layer was acidified with hydrochloric acid (2M) (2 ml) and washed with ethyl acetate (×2). The combined organic layers were washed with brine, dried over anhydrous sodium sulphate, filtered and the solvent was removed under reduced pressure. The oil was purified by column chromatography on silica gel eluting with a gradient system of 100:0:0 (dichloromethane:methanol:acetic acid) gradually changing to 90:10:1 (dichloromethane:methanol:acetic acid) to afford the title compound as an orange gum (36 mg).

Workup

  1. washwashed with diethylether (×2)
  2. washwashed with ethyl acetate (×2)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous sodium sulphate
  5. filtrationfiltered
  6. customthe solvent was removed under reduced pressure
  7. customThe oil was purified by column chromatography on silica gel eluting with a gradient system of 100:0:0 (dichloromethane:methanol:acetic acid)

Sources & evidence

ORD record
ord-2d479b1ab418493d816b985d6aed8445
Source dataset
uspto-grants-2002_09
Patent number
US06448278B2

Reaction notes

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