Diethyl Ether → 2-Chloro-5-fluoro-4-methylpyrimidine

HRID 243852Notes

Reaction equation

HRID 243852 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([F:9])=[CH:4][N:3]=1.[CH3:10][Mg]Br.CCOCC>C1COCC1.CN1C(=O)CCC1>[Cl:1][C:2]1[N:7]=[C:6]([CH3:10])[C:5]([F:9])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 178418573HCID 178418573, compound

Product 1

HCID 207780732-Chloro-5-fluoro-4-methylpyrimidineYield 48%

Reagents, catalysts & solvents 1

HCID 22156051tetrahydrofuran N-methylpyrrolidinoneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2,4-dichloro-5-fluoropyrimidine (1.02 g, 6.08 mmol) in THF/NMP (38 mL/3 mL) was added Fe(acac)3 (215 mg, 0.61 mmol) and the mixture was cooled to 0° C. 3.0 M methylmagnesium bromide in Et2O (3.04 mL, 9.12 mmol) was added dropwise. After 30 min at 0° C., the reaction was complete and quenched with saturated aqueous NH4Cl solution. Et2O was added and the layers were separated and the aqueous layer was further extracted with several portions of Et2O. The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. Chromatography (Hexanes to 10% EtOAc/Hexanes) gave the desired product as a waxy white solid (430 mg, 48%). 1H NMR (400 MHz, CDCl3): 8.35 (s, 1H), 2.55 (d, J=2.5 Hz, 3H).

Workup

  1. customquenched with saturated aqueous NH4Cl solution
  2. additionEt2O was added
  3. customthe layers were separated
  4. extractionthe aqueous layer was further extracted with several portions of Et2O
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2ee1a05bda75483fa10cb72713c77c73
Source dataset
uspto-grants-2014_02
Patent number
US08653263B2

Reaction notes

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