2-Bromopyridine → HCID 66875697, compound

HRID 1666513Notes

Reaction equation

HRID 1666513 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][CH:21]=1)[CH:5]=[C:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1.Br[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.CC#N.CC#N.CC#N.CC#N.F[P-](F)(F)(F)(F)F.[Cu+]>[C:15]([O:14][C:12]([N:9]1[CH2:8][CH2:7][C:6](=[CH:5][C:4]2[CH:19]=[CH:20][CH:21]=[C:2]([O:1][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=3)[CH:3]=2)[CH2:11][CH2:10]1)=[O:13])([CH3:18])([CH3:16])[CH3:17]

Participants

6

Reactant 3

HCID 79732-Bromopyridine2×HCID 10796Cesium carbonateHCID 53485958Tert-butyl 4-(3-hydroxybenzylidene)piperidine-1-carboxylate

Product 1

HCID 66875697HCID 66875697, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 11068737tetrakis(acetonitrile)copper(I) hexafluorophosphateCatalyst2×HCID 1140TolueneSolvent

Procedure

A mixture of tert-butyl 4-(3-hydroxybenzylidene)piperidine-1-carboxylate (0.300 g, Example 57, Step 3), 2-bromopyridine (0.253 mL, 1.50 equiv), cesium carbonate (1.13 g, 2.01 equiv), and tetrakis(acetonitrile)copper(I) hexafluorophosphate (0.048 g, 0.075 equiv) in toluene (9 mL, 0.2 M) was heated to reflux for 12 hours. Additional tetrakis(acetonitrile)copper(I) hexafluorophosphate (0.02 g) and 2-bromopyridine (0.1 mL) were added, and the reaction was heated an additional 6 hours. After cooling to room temperature, the reaction was filtered through Celite, washing the Celite with dichloromethane. The filtrate was concentrated and purified on 60 g silica gel using a gradient eluent consisting of 0-10% ethyl acetate/dichloromethane over 60 minutes to give the title compound as a white solid. 0.483 g, 76% yield. 1H NMR (400 MHz, CDCl3) δ ppm 1.45 (9H, s), 2.29 (2H, br. S.), 2.45 (2H, t, J=5.5 Hz), 3.37 (2H, t, J=5.4 Hz), 3.47 (2H, t, J=5.7 Hz), 6.32 (1H, s), 6.76-7.13 (5H, m), 7.32 (1H, t, J=7.7 Hz), 7.67 (1H, t, J=6.5 Hz), 8.18 (1H, br. s.).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 12 hours
  3. temperaturethe reaction was heated an additional 6 hours
  4. filtrationthe reaction was filtered through Celite
  5. washwashing the Celite with dichloromethane
  6. concentrationThe filtrate was concentrated
  7. custompurified on 60 g silica gel using a gradient eluent

Sources & evidence

ORD record
ord-d99cf0255f4b4dc0837427e92d72a689
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

Loading…