Cesium carbonate → 2-Cyclopropyl-4-methyl-5-nitropyridine

HRID 1527302Notes

Reaction equation

HRID 1527302 reaction equation
[CH:1]1([B-](F)(F)F)[CH2:3][CH2:2]1.[K+].Cl[C:10]1[CH:15]=[C:14]([CH3:16])[C:13]([N+:17]([O-:19])=[O:18])=[CH:12][N:11]=1.C([O-])([O-])=O.[Cs+].[Cs+].C(P(C12CC3CC(CC(C3)C1)C2)C12CC3CC(CC(C3)C1)C2)CCC>C(Cl)Cl.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:1]1([C:10]2[CH:15]=[C:14]([CH3:16])[C:13]([N+:17]([O-:19])=[O:18])=[CH:12][N:11]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 3453642-Chloro-4-methyl-5-nitropyridineHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneHCID 23697338Potassium cyclopropyltrifluoroborate2×

Product 1

HCID 682836712-Cyclopropyl-4-methyl-5-nitropyridine

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

Potassium cyclopropyltrifluoroborate (857 mg, 5.79 mmol), 2-chloro-4-methyl-5-nitropyridine (500 mg, 2.90 mmol), Pd(OAc)2 (26 mg, 0.12 mmol), Cs2CO3 (2.83 g, 8.69 mmol), and n-butyl-di-adamantylphosphine (62 mg, 0.17 mmol) were charged into a capped vial. The vial was purged with argon and then sealed with a septum cap. Toluene/H2O 10:1 (11 mL) was added by syringe and the mixture was heated at 100° C. for 16 h. More potassium cyclopropyltrifluoroborate (857 mg, 5.79 mmol) was added to the mixture which was further heated at 100° C. for 72 h. The mixture was diluted with CH2Cl2 and filtered through a pad of Celite. The filtrate was dried (Phase separator) and concentrated under reduced pressure. The residue was purified by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 30×100 mm, flow: 40 mL/min, eluent: 5-100% CH3CN/H2O/30 min, 100% CH3CN/3 min, CH3CN and H2O containing 0.1% TFA). MS (LC-MS): 179 [M+H]+, tR (HPLC conditions c): 4.26 min.

Workup

  1. customThe vial was purged with argon
  2. customsealed with a septum
  3. customcap
  4. additionToluene/H2O 10:1 (11 mL) was added by syringe
  5. temperaturewas further heated at 100° C. for 72 h
  6. filtrationfiltered through a pad of Celite
  7. customThe filtrate was dried (Phase separator)
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 30×100 mm, flow: 40 mL/min, eluent: 5-100% CH3CN/H2O/30 min, 100% CH3CN/3 min, CH3CN and H2O containing 0.1% TFA)
  10. custom4.26 min.

Sources & evidence

ORD record
ord-87cc3c11d761466491f024ee5dcb6df3
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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