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

HRID 2095698Notes

Reaction equation

HRID 2095698 reaction equation
[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

Participants

4

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-3128b62035064d35bc251a5c25235888
Source dataset
uspto-grants-2013_05
Patent number
US08445510B2

Reaction notes

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