Tetrahydrofuran → methyl (2S)-1-(6-isobutyl-1,3-benzoxazol-2-yl)-2-piperidinecarboxylate

HRID 1635663Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1635663
[CH2:1](B(O)O)[CH:2]([CH3:4])[CH3:3].C(=O)([O-])[O-].[K+].[K+].Br[C:15]1[CH:33]=[CH:32][C:18]2[N:19]=[C:20]([N:22]3[CH2:27][CH2:26][CH2:25][CH2:24][C@H:23]3[C:28]([O:30][CH3:31])=[O:29])[O:21][C:17]=2[CH:16]=1.O1CCCC1>C1(C)C=CC=CC=1>[CH2:1]([C:15]1[CH:33]=[CH:32][C:18]2[N:19]=[C:20]([N:22]3[CH2:27][CH2:26][CH2:25][CH2:24][C@H:23]3[C:28]([O:30][CH3:31])=[O:29])[O:21][C:17]=2[CH:16]=1)[CH:2]([CH3:4])[CH3:3]

Komponenten

6

Edukt 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 2734395(2-Methylpropyl)boronic acidHCID 9949771methyl (2S)-1-(6-bromo-1,3-benzoxazol-2-yl)-2-piperidinecarboxylate

Produkt 1

HCID 9839924methyl (2S)-1-(6-isobutyl-1,3-benzoxazol-2-yl)-2-piperidinecarboxylateAusbeute 13,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

Isobutyl boronic acid (475 mg), potassium carbonate (644 mg) and tetrakis triphenylphosphine palladium (269 mg) were added sequentially to a solution of methyl (2S)-1-(6-bromo-1,3-benzoxazol-2-yl)-2-piperidinecarboxylate (790 mg) [see Preparation 40] in toluene:tetrahydrofuran, 60:40 by volume, (20 ml) under nitrogen. The reaction mixture was then heated to 80° C. for 20 hours, after which time the solvent was removed under reduced pressure and the residue partitioned between water and dichloromethane. The organic layer was separated and washed with water, dried over magnesium sulphate and the solvent removed under reduced pressure. The crude product was purified by column chromatography on silica gel eluting with a solvent system of 80:20, by volume, hexane:ethyl acetate to afford methyl (2S)-1-(6-isobutyl-1,3-benzoxazol-2-yl)-2-piperidinecarboxylate (100 mg) as an oil.

Aufarbeitung

  1. customafter which time the solvent was removed under reduced pressure
  2. customthe residue partitioned between water and dichloromethane
  3. customThe organic layer was separated
  4. washwashed with water
  5. dry with materialdried over magnesium sulphate
  6. customthe solvent removed under reduced pressure
  7. customThe crude product was purified by column chromatography on silica gel eluting with a solvent system of 80:20, by volume, hexane

Quellen und Nachweise

ORD-Eintrag
ord-3fedb8ea58d04c7eb06cf2b8c2df028e
Quelldatensatz
uspto-grants-2003_01
Patentnummer
US06509464B1

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