Reaktion #2270119

Reaktionsgleichung

O-(Trimethylsilyl)hydroxylamine

(3R)-6-cyclohexyl-3-(3-{[(2-methoxy-2-oxoethyl)(methyl)amino]carbonyl}-1,2,4-oxadiazol-5-yl)hexanoic acid

N-methylmorpholine

isobutyl chloroformate

→

title compound

Ausbeute 65.1%

Methyl 2-[[(5-{(1R)-4-cyclohexyl-1-[2-(hydroxyamino)-2-oxoethyl]butyl}-1,2,4-oxadiazol-3-yl)carbonyl](methyl)amino]acetate

Ausbeute 65.1%

Lösungsmittel

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe mixture stirred under a nitrogen atmosphere for 1 hour
2. 2
   SonstigeThe mixture was then quenched with methanol (10 ml)
3. 3
   workup.STIRRINGstirred for 10 minutes
4. 4
   SonstigeThe solvent was removed under reduced pressure
5. 5
   Sonstigethe residue partitioned between ethyl acetate and water
6. 6
   SonstigeThe layers were separated
7. 7
   Waschenthe organic layer was sequentially washed with water and brine
8. 8
   Trocknendried over anhydrous sodium sulphate
9. 9
   Filtrationfiltered
10. 10
    Sonstigethe solvent removed under reduced pressure
11. 11
    SonstigeThe residue was purified by HPLCa

Vorschrift

A solution of (3R)-6-cyclohexyl-3-(3-{[(2-methoxy-2-oxoethyl)(methyl)amino]carbonyl}-1,2,4-oxadiazol-5-yl)hexanoic acid (Preparation 39) (273 mg, 0.70 mmol)and N-methylmorpholine (85 μl, 0.77 mmol) in anhydrous dichloromethane (10 ml) was cooled to 0° C., treated with isobutyl chloroformate (100 μl, 0.77 mmol) and the resulting mixture was stirred under a nitrogen atmosphere for 30 minutes. O-(Trimethylsilyl)hydroxylamine (250 μl, 2.10 mmol) was then added and the mixture stirred under a nitrogen atmosphere for 1 hour, being allowed to warm to room temperature over this time. The mixture was then quenched with methanol (10 ml) and stirred for 10 minutes. The solvent was removed under reduced pressure and the residue partitioned between ethyl acetate and water. The layers were separated and the organic layer was sequentially washed with water and brine, dried over anhydrous sodium sulphate, filtered and the solvent removed under reduced pressure. The residue was purified by HPLCa to afford the title compound as a colourless oil (187 mg).

Quelle