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Piperidine → tert-butyl 5-bromo-3-[(1S)-1-(2-chloro-3-fluoro-6-hydroxyphenyl)ethyl]-1H-pyrrolo[2,3-b]pyridine-1-carboxylate

HRID 2095698
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Reaktionsgleichung von HRID 2095698
[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([C@@H:11]([C:13]3[C:18]([O:19]C(OC(C)(C)C)=O)=[CH:17][CH:16]=[C:15]([F:27])[C:14]=3[Cl:28])[CH3:12])=[CH:9][N:8]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C:5]2=[N:6][CH:7]=1.N1CCCCC1>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([C@@H:11]([C:13]3[C:18]([OH:19])=[CH:17][CH:16]=[C:15]([F:27])[C:14]=3[Cl:28])[CH3:12])=[CH:9][N:8]([C:29]([O:31][C:32]([CH3:33])([CH3:35])[CH3:34])=[O:30])[C:5]2=[N:6][CH:7]=1
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Edukt 2

HCID 8082PiperidineHCID 67004479tert-butyl 5-bromo-3-[(1S)-1-{6-[(tert-butoxycarbonyl)oxy]-2-chloro-3-fluorophenyl}ethyl]-1H-pyrrolo[2,3-b]pyridine-1-carboxylate

Produkt 1

HCID 67003938tert-butyl 5-bromo-3-[(1S)-1-(2-chloro-3-fluoro-6-hydroxyphenyl)ethyl]-1H-pyrrolo[2,3-b]pyridine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

A solution of tert-butyl 5-bromo-3-[(1S)-1-{6-[(tert-butoxycarbonyl)oxy]-2-chloro-3-fluorophenyl}ethyl]-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (1.982 g, 3.478 mmol) in CH2Cl2 (40 mL) was charged with piperidine (12 mL, 120 mmol) and was stirred at rt for 16 h. The reaction mixture was diluted with CH2Cl2 and washed with 0.5 N HCl (4×50 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The crude was adsorbed onto a pre-filled silica gel loading cartridge [RediSepRf, 5 g] and purified using the Teledyne/ISCO system [RediSepRf 24 gram silica], eluting with a 10-50% EtOAc:Heptane solvent gradient. Fractions containing the desired product were pooled together and concentrated in vacuo, yielding the title material as a white solid. 1H NMR (400 MHz, CDCl3): δ=8.39 (d, J=2.3 Hz, 1H), 7.65 (d, J=1.5 Hz, 1H), 7.54 (d, J=2.0 Hz, 1H), 6.97 (dd, J=8.8, 8.3 Hz, 1H), 6.67 (dd, J=8.8, 4.5 Hz, 1H), 4.93 (qd, J=7.1, 1.3 Hz, 1H), 1.78 (d, J=7.1 Hz, 3H), 1.68 (s, 9H). MS (ES+): m/z 412.78/414.75/416.76 (75/100/27) [MH+−C4H8]. HPLC: tR=4.13 min (ZQ3, polar—5 min).

Aufarbeitung

  1. washwashed with 0.5 N HCl (4×50 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. custompurified
  7. washeluting with a 10-50% EtOAc
  8. additionFractions containing the desired product
  9. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-3128b62035064d35bc251a5c25235888
Quelldatensatz
uspto-grants-2013_05
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08445510B2

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