Cesium carbonate → 3-Bromo-5-cyclopropyl-4-methylpyridine

HRID 530014Notes

Reaction equation

HRID 530014 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:8]1[CH:9]=[N:10][CH:11]=[C:12]([Br:15])[C:13]=1[CH3:14].[CH:16]1(B(O)O)[CH2:18][CH2:17]1.O1CCOCC1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[Br:15][C:12]1[CH:11]=[N:10][CH:9]=[C:8]([CH:16]2[CH2:18][CH2:17]2)[C:13]=1[CH3:14]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 8193383,5-Dibromo-4-methylpyridineHCID 2760897Cyclopropylboronic acid

Product 1

HCID 709781453-Bromo-5-cyclopropyl-4-methylpyridine

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

Cesium carbonate (2.59 g, 0.00797 mol) was added to a stirred solution of 3,5-dibromo-4-methylpyridine (1.0 g, 0.0039 mol) and cyclopropylboronic acid (0.34 g, 0.0039 mol) in the mixture of 1,4-dioxan (35 mL) and water (15 mL). The reaction mixture was purged with argon for 20 min. Next, Pd(dppf)2Cl2 (0.14 g, 0.000199 mol) was added. The reaction mixture was heated at 100° C. and for 6 h. It was cooled to room temperature, filtered through a bed of CELITE and the bed was thoroughly washed with ethyl acetate. The filtrate was concentrated under vacuum. The residue was dissolved with dichloromethane, washed with water and saturated sodium chloride solution, dried over sodium sulphate, concentrated under vacuum and purified by silica gel (60-120) column chromatography with 0-2.5% ethyl acetate in hexane to afford the title compound. 1H NMR (400 MHz, CdCl3) δ 8.51 (s, 1 H), 8.17 (s, 1 H), 2.52 (s, 3 H), 1.87-1.82 (m, 1 H), 1.03-0.99 (m, 2 H), 0.71-0.68 (m, 2 H). MS (M+1): 211.8.

Workup

  1. customThe reaction mixture was purged with argon for 20 min
  2. temperatureIt was cooled to room temperature
  3. filtrationfiltered through a bed of CELITE
  4. washthe bed was thoroughly washed with ethyl acetate
  5. concentrationThe filtrate was concentrated under vacuum
  6. dissolutionThe residue was dissolved with dichloromethane
  7. washwashed with water and saturated sodium chloride solution
  8. dry with materialdried over sodium sulphate
  9. concentrationconcentrated under vacuum
  10. custompurified by silica gel (60-120) column chromatography with 0-2.5% ethyl acetate in hexane

Sources & evidence

ORD record
ord-835d0044cd694a8b8ee815ed0388fae4
Source dataset
uspto-grants-2016_05
Patent number
US09351973B2

Reaction notes

Loading…