2-Bromopyridine → HCID 66687133, compound

HRID 2089106Notes

Reaction equation

HRID 2089106 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[Li]CCCC.[C:13]([N:20]1[CH2:25][CH2:24][CH:23](C#N)[CH2:22][CH2:21]1)([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14].C1C[O:31][CH2:30]C1>O>[N:3]1[CH:4]=[CH:5][C:6]([C:30]([CH:25]2[CH2:24][CH2:23][CH2:22][CH2:21][N:20]2[C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])=[O:31])=[CH:7][CH:2]=1

Participants

6

Reactant 4

HCID 79732-BromopyridineHCID 8028Tetrahydrofuran2×HCID 1514443Tert-butyl 4-cyanopiperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 66687133HCID 66687133, compoundYield 18%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 2-bromopyridine (3.60 g, 22.5 mmol) in THF (100 mL) at −78° C. was added n-BuLi (1.6 M in hexanes, 20.0 mL, 22.5 mmol) and stirred for 1.5 h. Added a solution of 1-N-Boc-4-cyanopiperidine (4.60 g, 21.9 mmol) in THF (50 mL) and stirred for 18 h whilst warming to room temperature. The reaction was diluted with water (400 mL) and extracted with EtOAc (2×400 mL). The combined organic extracts were dried over MgSO4, concentrated under vacuum and purified by column chromatography using 0 to 40% EtOAc in hexanes to afford 6 a clear pale yellow oil (1.01 g, 18%); 1H-nmr (400 MHz, CDCl3) δ 8.68 (d, J=5.0 Hz, 1H), 8.04 (d, J=8.0 Hz, 1H), 7.85 (td, J=8.0, 1.5 Hz, 1H), 7.48 (dd, J=8.0, 1.5 Hz, 1H), 4.21-4.07 (m, 2H), 4.02 (tt, J=11.0, 3.5 Hz, 1H), 2.93 (t, J=11.0 Hz, 2H), 1.89 (d, J=9.5 Hz, 2H), 1.71-1.60 (m, 2H), 1.48 (s, 9H); m/z 232.8 [M-tBu].

Workup

  1. stirringstirred for 18 h
  2. extractionextracted with EtOAc (2×400 mL)
  3. dry with materialThe combined organic extracts were dried over MgSO4
  4. concentrationconcentrated under vacuum
  5. custompurified by column chromatography

Sources & evidence

ORD record
ord-9e3c0a031bef47d28ac935f7a7af3a69
Source dataset
uspto-grants-2013_05
Patent number
US08436019B2

Reaction notes

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