Citric Acid → (R)-5-(6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl)-N-methyl-1,2,4-oxadiazole-3-carboxamide

HRID 2182910Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2182910
[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:15]2[O:19][N:18]=[C:17]([C:20]([NH:22][CH3:23])=[O:21])[N:16]=2)[CH2:11][C:12](O)=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CN1CCOCC1.ClC(OCC(C)C)=O.C[Si](C)(C)[O:41][NH2:42].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1.O>[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:15]2[O:19][N:18]=[C:17]([C:20]([NH:22][CH3:23])=[O:21])[N:16]=2)[CH2:11][C:12]([NH:42][OH:41])=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Komponenten

8

Edukt 5

HCID 311Citric AcidHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 2734666O-(Trimethylsilyl)hydroxylamineHCID 59909843(3R)-6-cyclohexyl-3-{3-[(methylamino)carbonyl]-1,2,4-oxadiazol-5-yl}hexanoic acid

Produkt 1

HCID 9902427(R)-5-(6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl)-N-methyl-1,2,4-oxadiazole-3-carboxamideAusbeute 43,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A solution of (3R)-6-cyclohexyl-3-{3-[(methylamino)carbonyl]-1,2,4-oxadiazol-5-yl}hexanoic acid (Preparation 8) (285 mg, 0.88 mmol) and N-methylmorpholine (110 μl, 1.00 mmol) in anhydrous tetrahydrofuran (10 ml) was cooled to 0° C., treated with isobutyl chloroformate (130 μl, 1.00 mmol) and stirred under a nitrogen atmosphere for 1 hour. O-(Trimethylsilyl)hydroxylamine (130 μl, 1.06 mmol) was added and the mixture was stirred for 18 hours, being allowed to warm to room temperature over this time. The mixture was then treated with aqueous citric acid solution (10% w/v, 10 ml) and stirred for 2 hours. This mixture was diluted with water and extracted with ethyl acetate (×3). The combined organic layers were washed sequentially with water and brine, dried over anhydrous sodium sulphate, filtered and the solvent removed under reduced pressure. The solid was then recrystallised from hexane:ethyl acetate to afford the title compound as a white solid (130 mg).

Aufarbeitung

  1. stirringthe mixture was stirred for 18 hours
  2. stirringstirred for 2 hours
  3. extractionextracted with ethyl acetate (×3)
  4. washThe combined organic layers were washed sequentially with water and brine
  5. dry with materialdried over anhydrous sodium sulphate
  6. filtrationfiltered
  7. customthe solvent removed under reduced pressure
  8. customThe solid was then recrystallised from hexane

Quellen und Nachweise

ORD-Eintrag
ord-9ed1652f00c94c61875e4afa6fb023b6
Quelldatensatz
uspto-grants-2005_05
Patentnummer
US06897306B2

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