Cesium carbonate → tert-butyl 4-{3-[(3R)-3-({(1S)-3-tert-butoxy-1-[5-(2-fluoroethoxy)pyridin-3-yl]-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylat

HRID 526320

Reaktionsgleichung

Reaktionsgleichung von HRID 526320
[C:1]([O:5][C:6](=[O:42])[CH2:7][C@H:8]([NH:16][C:17]([C@@H:19]1[CH2:24][CH2:23][CH2:22][N:21]([C:25](=[O:41])[CH2:26][CH2:27][CH:28]2[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29]2)[CH2:20]1)=[O:18])[C:9]1[CH:10]=[N:11][CH:12]=[C:13]([OH:15])[CH:14]=1)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[F:49][CH2:50][CH2:51]OS(C1C=CC(C)=CC=1)(=O)=O>CN(C)C=O>[C:1]([O:5][C:6](=[O:42])[CH2:7][C@H:8]([NH:16][C:17]([C@@H:19]1[CH2:24][CH2:23][CH2:22][N:21]([C:25](=[O:41])[CH2:26][CH2:27][CH:28]2[CH2:29][CH2:30][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:32][CH2:33]2)[CH2:20]1)=[O:18])[C:9]1[CH:10]=[N:11][CH:12]=[C:13]([O:15][CH2:51][CH2:50][F:49])[CH:14]=1)([CH3:3])([CH3:2])[CH3:4]

Komponenten

5

Edukt 3

HCID 10796Cesium carbonate2×HCID 2560192-Fluoroethyl p-Toluenesulfonate2×HCID 71259825Tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-(5-hydroxypyridin-3-yl)-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

Produkt 1

HCID 71609266tert-butyl 4-{3-[(3R)-3-({(1S)-3-tert-butoxy-1-[5-(2-fluoroethoxy)pyridin-3-yl]-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylatAusbeute 77,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

Tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-(5-hydroxypyridin-3-yl)-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate (example 25e, 800 mg, 1.36 mmol) was dissolved in N,N-dimethylformamide (52 mL). Cesium carbonate (1.1 g, 3.4 mmol) and 2-fluoroethyltosylat (445 mg, 2.04 mmol) were added. The mixture was stirred at room temperature for 3.5 hours, additional cesium carbonate (70 mg, 0.21 mmol) and 2-fluoroethyltosylate (28 mg, 0.13 mmol) were added and stirring was continued for 2.5 hours at room temperature and 17 hours at 5° C. The mixture was quenched by addition of saturated aqueous ammonium chloride solution and extracted with diethyl ether and ethyl acetate. The combined extracts were washed with brine and dried over sodium sulfate. The solution was concentrated under reduced pressure and the residue was purified by chromatography on silica gel (ethyl acetate in hexane 20 to 100% followed by dioxane in ethyl acetate 0 to 50%) to yield 670 mg of tert-butyl 4-{3-[(3R)-3-({(1S)-3-tert-butoxy-1-[5-(2-fluoroethoxy)pyridin-3-yl]-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylat.

Aufarbeitung

  1. stirringstirring
  2. waitwas continued for 2.5 hours at room temperature and 17 hours at 5° C
  3. customThe mixture was quenched by addition of saturated aqueous ammonium chloride solution
  4. extractionextracted with diethyl ether and ethyl acetate
  5. washThe combined extracts were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationThe solution was concentrated under reduced pressure
  8. customthe residue was purified by chromatography on silica gel (ethyl acetate in hexane 20 to 100% followed by dioxane in ethyl acetate 0 to 50%)

Quellen und Nachweise

ORD-Eintrag
ord-7a035a0a22944abc9bcf85cbd36655b8
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09345793B2

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