Potassium Carbonate → (R)-4-[(S)-1-(6-cyano-3,3-dimethyl-2,3-dihydro-indole-1-carbonyl)-propyl]-2-methyl-piperazine-1-carboxylic acid tert-butyl ester

HRID 1475534Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1475534
Cl[C@H:2]([CH2:18][CH3:19])[C:3]([N:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]#[N:15])[CH:12]=2)[C:7]([CH3:17])([CH3:16])[CH2:6]1)=[O:4].[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][NH:30][CH2:29][C@H:28]1[CH3:33])=[O:26])([CH3:23])([CH3:22])[CH3:21].C(=O)([O-])[O-].[K+].[K+]>C(#N)C.C(OCC)(=O)C>[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][N:30]([C@H:2]([C:3]([N:5]2[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([C:14]#[N:15])[CH:12]=3)[C:7]([CH3:17])([CH3:16])[CH2:6]2)=[O:4])[CH2:18][CH3:19])[CH2:29][C@H:28]1[CH3:33])=[O:26])([CH3:23])([CH3:21])[CH3:22]

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 10262201tert-Butyl (2R)-2-methylpiperazine-1-carboxylateHCID 86724047(R)-1-(2-chlorobutanoyl)-3,3-dimethylindoline-6-carbonitrile

Produkt 1

HCID 70981673(R)-4-[(S)-1-(6-cyano-3,3-dimethyl-2,3-dihydro-indole-1-carbonyl)-propyl]-2-methyl-piperazine-1-carboxylic acid tert-butyl esterAusbeute 14,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6342AcetonitrileLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To a suspension of (R)-1-(2-chlorobutanoyl)-3,3-dimethylindoline-6-carbonitrile (0.1 g, 0.36 mmol), (R)-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (0.072 g, 0.36 mmol) in acetonitrile (2.5 mL) was added potassium carbonate (0.049 g, 0.36 mmol) and the reaction heated to 50° C. for 48 h followed by 80° C. for 24 h and 60° C. for 36 h. The reaction mixture was then diluted with ethyl acetate and washed with water. The organics were separated, dried with sodium sulfate and concentrated. The residue was purified by flash column chromatography on silica gel; eluting with 20-30% ethyl acetate in heptane to give (R)-4-[(S)-1-(6-cyano-3,3-dimethyl-2,3-dihydro-indole-1-carbonyl)-propyl]-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (0.023 g). MS: [M+H]+=441.

Aufarbeitung

  1. washwashed with water
  2. customThe organics were separated
  3. dry with materialdried with sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by flash column chromatography on silica gel
  6. washeluting with 20-30% ethyl acetate in heptane

Quellen und Nachweise

ORD-Eintrag
ord-d1e78516d6b64755b484878cdbf28048
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09018214B2

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