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

HRID 1521558Notes

Reaction equation

HRID 1521558 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:9])[C:7]=1[CH3:8].[CH:10]1(B(O)O)[CH2:12][CH2:11]1.O1CCOCC1.C(=O)([O-])[O-].[Cs+].[Cs+]>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:9][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([CH:10]2[CH2:12][CH2:11]2)[C:7]=1[CH3:8]

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

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) was added cesium carbonate (2.59 g, 0.00797 mol). Reaction mass was purging with argon for the 20 min. After 20 min, Pd(dppf)2Cl2 (0.14 g, 0.000199 mol) was added. The reaction mixture was heated to 100° C. and stirred for 6 h. The reaction mixture was cooled to room temperature, filtered the reaction mixture through CELITE bed and the CELITE bed was thoroughly washed with ethyl acetate. The filtrate was concentrated under vacuum. The residue was dissolved with dichloromethane and washed with water, saturated aqueous sodium chloride solution, dried over sodium sulphate, concentrated under vacuum, which was purified with silica gel (60-120) column chromatography by 0-2.5% ethyl acetate in hexane to afford the title compound (IN-14). 1H NMR (400 MHz, CdCl3) δ 8.51 (s, 1H), 8.17 (s, 1H), 2.52 (s, 3H), 1.87-1.82 (m, 1H), 1.03-0.99 (m 2H), 0.71-0.68 (m, 2H). MS (M+1): 211.8.

Workup

  1. customReaction mass
  2. customwas purging with argon for the 20 min
  3. temperatureThe reaction mixture was cooled to room temperature
  4. filtrationfiltered the reaction mixture through CELITE bed
  5. washthe CELITE bed was thoroughly washed with ethyl acetate
  6. concentrationThe filtrate was concentrated under vacuum
  7. dissolutionThe residue was dissolved with dichloromethane
  8. washwashed with water, saturated aqueous sodium chloride solution
  9. dry with materialdried over sodium sulphate
  10. concentrationconcentrated under vacuum, which
  11. customwas purified with silica gel (60-120) column chromatography by 0-2.5% ethyl acetate in hexane

Sources & evidence

ORD record
ord-7417fe2ee3084928b216eae59fc36882
Source dataset
uspto-grants-2015_07
Patent number
US09073929B2

Reaction notes

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