Piperidine → HCID 57545919, Verbindung

HRID 913845

Reaktionsgleichung

Reaktionsgleichung von HRID 913845
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH:11]([O:13][CH2:14][C:15]3([C:28]4[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=4)[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]3)[CH3:12])[CH:10]=1)[N:7](COCC[Si](C)(C)C)[N:6]=[CH:5]2.N1CCCCC1.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O>FC(F)(F)C(O)=O.ClCCl>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH:11]([O:13][CH2:14][C:15]3([C:28]4[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=4)[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:26])([CH3:27])[CH3:25])=[O:22])[CH2:17][CH2:16]3)[CH3:12])[CH:10]=1)[NH:7][N:6]=[CH:5]2

Komponenten

6

Edukt 3

HCID 8082PiperidineHCID 90495Di-tert-butyl dicarbonateHCID 57545992(+/-)-tert-Butyl 4-((1-(5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

Produkt 1

HCID 57545919HCID 57545919, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 6422Trifluoroacetic acidLösungsmittel

Versuchsvorschrift

(±)-tert-Butyl 4-((1-(5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (543 mg, 0.819 mmol) was dissolved in trifluoroacetic acid (50% in dichloromethane, 10 mL) and stirred at room temperature for 4 h. The reaction was concentrated and loaded onto a strong cation exchange cartridge in methanol. After washing with several volumes of methanol, the product was eluted with 2M ammonia in methanol. Concentration gave the crude piperidine. The piperidine was dissolved in dichloromethane (5 mL) and treated with di-tert-butyl dicarbonate (224 mg, 1.02 mmol). After 1 h, the reaction was quenched by addition of 2M ammonia in methanol and concentrated. The residue was suspended in water and extracted with diethyl ether. The ethereal was washed with water, then brine, dried over magnesium sulfate, and concentrated. Column chromatography (EtOAc/Hex) gave 420 mg (96%). 1H-NMR (CDCl3, 500 MHz) δ 10.05 (bs, 1H), 7.89 (s, 1H), 7.71 (d, J=1.8, 1H), 7.23 (m, 2H), 7.08 (d, J=1.5, 1H), 7.02 (m, 2H), 4.48 (q, J=6.7, 1H), 3.70 (m, 2H), 3.34 (d, J=9.2, 1H), 3.23 (d, J=8.9, 1H), 3.03 (m, 1H), 2.95 (m, 1H), 2.21 (m, 1H), 2.03 (m, 1H), 1.82 (m, 1H), 1.72 (m, 1H), 1.41 (s, 9H), 1.40 (d, J=6.7, 3H); 13C NMR (126 MHz, CDCl3) δ ppm 162.6, 160.6, 155.0, 138.1, 135.9, 133.7, 128.7 (d, J=7.7), 127.9, 126.5, 125.5, 122.3, 115.7, 115.6, 113.6, 79.6, 78.6, 78.0, 41.2, 40.1, 32.5, 32.1, 28.5, 22.2, 14.3.

Aufarbeitung

  1. concentrationThe reaction was concentrated
  2. washAfter washing with several volumes of methanol
  3. washthe product was eluted with 2M ammonia in methanol
  4. concentrationConcentration
  5. customgave the crude piperidine
  6. waitAfter 1 h
  7. customthe reaction was quenched by addition of 2M ammonia in methanol
  8. concentrationconcentrated
  9. extractionextracted with diethyl ether
  10. washThe ethereal was washed with water
  11. dry with materialbrine, dried over magnesium sulfate
  12. concentrationconcentrated
  13. customColumn chromatography (EtOAc/Hex) gave 420 mg (96%)

Quellen und Nachweise

ORD-Eintrag
ord-9850382c78b94810a560608fc5918e6e
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08026257B2

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