Acetic Acid → 2-Chloro-4-ethyl-5-fluoropyrimidine

HRID 634235Notes

Reaction equation

HRID 634235 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8](C)(C(OCC)=O)[C:9](OCC)=O)[C:5]([F:20])=[CH:4][N:3]=1.CC(O)=O.Cl.O>C(Cl)Cl>[Cl:1][C:2]1[N:7]=[C:6]([CH2:8][CH3:9])[C:5]([F:20])=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 962WaterHCID 86725111Diethyl 2-(2-chloro-5-fluoropyrimidin-4-yl)-2-methylmalonate

Product 1

HCID 190749282-Chloro-4-ethyl-5-fluoropyrimidineYield 21%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

Diethyl 2-(2-chloro-5-fluoropyrimidin-4-yl)-2-methylmalonate (3.00 g, 9.85 mmol) was treated with glacial HOAc (25 mL) and 5N HCl (10 mL) and fitted with a reflux condenser and heated to 100° C. for 18 h. The reaction was cooled to RT and treated with H2O (30 mL) and DCM (45 mL) and the DCM layer separated and dried over MgSO4, filtered and concentrated. The crude residue was purified with flash chromatography (eluting with 100% DCM) affording 2-chloro-4-ethyl-5-fluoropyrimidine (328 mg, 21%) as a viscous pale yellow oil. MS (ESI, pos. ion) m/z: 161.0 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 8.34 (1H, s), 2.87 (2H, qd, J=7.6, 2.0 Hz), 1.29-1.37 (3H, t).

Workup

  1. customfitted with a reflux condenser
  2. temperatureThe reaction was cooled to RT
  3. customthe DCM layer separated
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was purified with flash chromatography (eluting with 100% DCM)

Sources & evidence

ORD record
ord-96c5fb475b344b1ba0e448a7f82a6f8b
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

Loading…