Tetrahydrofuran → 4-(8-Chloro-quinolin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester

HRID 719535Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 719535
[H-].[Na+].[CH:3]([O:6][C:7]([N:9]1[CH2:14][CH2:13][CH:12]([OH:15])[CH2:11][CH2:10]1)=[O:8])([CH3:5])[CH3:4].C1COCC1.Cl[C:22]1[C:31]2[C:26](=[C:27]([Cl:32])[CH:28]=[CH:29][CH:30]=2)[N:25]=[CH:24][CH:23]=1>C(Cl)Cl>[CH:3]([O:6][C:7]([N:9]1[CH2:10][CH2:11][CH:12]([O:15][C:22]2[C:31]3[C:26](=[C:27]([Cl:32])[CH:28]=[CH:29][CH:30]=3)[N:25]=[CH:24][CH:23]=2)[CH2:13][CH2:14]1)=[O:8])([CH3:5])[CH3:4]

Komponenten

6

Edukt 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 889734,8-DichloroquinolineHCID 16745126Isopropyl 4-Hydroxypiperidine-1-carboxylate

Produkt 1

HCID 574963804-(8-Chloro-quinolin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

In a 50 mL round-bottomed flask equipped with a N2 inlet septum was placed a stir bar, NaH (60% in mineral oil, 1.1 g, 30 mmol) and 4-hydroxy-piperidine-1-carboxylic acid isopropyl ester (0.93 g, 5 mmol). THF (anhydrous, 20 mL) was added to the mixture. The resulting suspension was stirred about 30 min at room temperature. 4,8-Dichloro-quinoline (1 g, 0.5 mmol) was then added in one portion. The mixture was stirred overnight under N2 at 80° C. and the resulting slurry turned slightly yellowish. The slurry was added CH2Cl2 and filtered. The filtrate was concentrated under vacuum to give the crude product. Purification by column chromatography gave 4-(8-chloro-quinolin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester as an off-white solid. 1H NMR (CDCl3, 400 MHz) δ 1.26 (d, 6H), 1.97 (m, 2H), 2.05 (m, 2H), 3.58 (m, 2H), 3.73 (m, 2H), 4.82 (m, 1H), 4.94 (m, 1H), 6.81 (d, 1H), 7.42 (t, 1H), 7.84 (d, 1H), 8.16 (d, 1H), 8.87 (d, 1H). Exact mass calculated for C18H21ClN2O3 348.12, found 349.2 (MH+)

Aufarbeitung

  1. customIn a 50 mL round-bottomed flask equipped with a N2 inlet septum
  2. stirringThe mixture was stirred overnight under N2 at 80° C.
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated under vacuum
  5. customto give the crude product
  6. customPurification by column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-7c25a98bccd2442eba46385407bb4ef7
Quelldatensatz
uspto-grants-2006_11
Patentnummer
US07132426B2

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