Methanol → Cyclopropyl-[4-((S)-2-methyl-piperazin-1-yl)-piperidin-1-yl]-methanone

HRID 1500514Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1500514
C(OC([N:8]1[CH2:13][CH2:12][NH:11][C@@H:10]([CH3:14])[CH2:9]1)=O)(C)(C)C.[CH:15]1([C:18]([N:20]2[CH2:25][CH2:24][C:23](=O)[CH2:22][CH2:21]2)=[O:19])[CH2:17][CH2:16]1.CO.C([BH3-])#N.[Na+]>FC(F)(F)C(O)=O>[CH:15]1([C:18]([N:20]2[CH2:25][CH2:24][CH:23]([N:11]3[CH2:12][CH2:13][NH:8][CH2:9][C@@H:10]3[CH3:14])[CH2:22][CH2:21]2)=[O:19])[CH2:16][CH2:17]1

Komponenten

6

Edukt 4

HCID 887MethanolHCID 5003444Sodium cyanoborohydrideHCID 7023035(S)-1-Boc-3-methylpiperazineHCID 149949681-Cyclopropanecarbonylpiperidin-4-one

Produkt 1

HCID 86700507Cyclopropyl-[4-((S)-2-methyl-piperazin-1-yl)-piperidin-1-yl]-methanoneAusbeute 141,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6422Trifluoroacetic acidKatalysator

Versuchsvorschrift

To a mixture of (S)-3-methyl-piperazine-1-carboxylic acid tert-butyl ester (220 mg, 1.1 mmol) and 1-(cyclopropylcarbonyl)piperidin-4-one (150 mg, 0.9 mmol) in methanol (5 mL, 120 mmol) was added slowly trifluoroacetic acid (6.9 μL, 0.09 mmol) followed by sodium cyanoborohydride (56 mg, 0.9 mmol). The reaction mixture was stirred overnight at RT, concentrated by rotary evaporation, washed with 1 N NaOH (20 mL) and extracted with EtOAc (3×15 mL). Combined organic fractions were washed with brine, dried with sodium sulfate, and concentrated by rotary evaporation to afford a white solid (320 mg). A mixture of the white solid in 4 M HCl in 1,4-dioxane (5 mL) was stirred at RT for 30 min and concentrated to provide the di-HCl salt of the title intermediate (180 mg, 62% yield) as a white suspension.

Aufarbeitung

  1. concentrationconcentrated by rotary evaporation
  2. washwashed with 1 N NaOH (20 mL)
  3. extractionextracted with EtOAc (3×15 mL)
  4. washCombined organic fractions were washed with brine
  5. dry with materialdried with sodium sulfate
  6. concentrationconcentrated by rotary evaporation

Quellen und Nachweise

ORD-Eintrag
ord-77cfb4ec9869432ca8eb6cbf828ca6f8
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09206159B2

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