Water → 5-Bromo-4-cyclopropylpyrimidine

HRID 871126Notes

Reaction equation

HRID 871126 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[N:6][CH:7]=1.[CH:8]1([Mg]Br)[CH2:10][CH2:9]1.O.C(C1C(=O)C(Cl)=C(Cl)C(=O)C=1C#N)#N>CCOCC.C1COCC1>[Br:1][C:2]1[C:3]([CH:8]2[CH2:10][CH2:9]2)=[N:4][CH:5]=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 783445-BromopyrimidineHCID 178418630HCID 178418630, compound

Product 1

HCID 536459075-Bromo-4-cyclopropylpyrimidineYield 20%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 5-bromopyrimidine (3 g, 18.87 mmol) in Et2O (120 mL) and THF (20 ml) was added cyclopropylmagnesium bromide (39.6 mL, 19.81 mmol) at 0° C. The resulting white suspension was stirred at room temperature for 1 h and quenched with water (0.340 mL, 18.87 mmol) followed by addition of DDQ (4.28 g, 18.87 mmol) in THF (10 ml). The resulting black mixture was stirred at room temperature overnight. The reaction mixture was extracted with EtOAc. The aqueous layer was extracted with EtOAc and the combined organic layer was washed with NaOH (1N) and brine. The crude product was purified by BIOTAGE® (0-15% EtOAc/hexanes, 1.2 L) to afford the title compound (700 mg, 20%) as a yellow solid. 1H NMR (500 MHz, chloroform-d) δ ppm 8.87 (1 hr, s), 8.66 (1 hr, s), 2.40-2.56 (1 hr, m), 1.13-1.32 (4 hr, m).

Workup

  1. stirringThe resulting black mixture was stirred at room temperature overnight
  2. extractionThe reaction mixture was extracted with EtOAc
  3. extractionThe aqueous layer was extracted with EtOAc
  4. washthe combined organic layer was washed with NaOH (1N) and brine
  5. customThe crude product was purified by BIOTAGE® (0-15% EtOAc/hexanes, 1.2 L)

Sources & evidence

ORD record
ord-fcb48968ec4d4479b3e12d17bac3b60d
Source dataset
uspto-grants-2015_03
Patent number
US08969586B2

Reaction notes

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