Thiophene → 2-Chloro-4-methyl-6-(2-thienyl)pyrimidine

HRID 1251475Notes

Reaction equation

HRID 1251475 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.C([Li])CCC.[Cl:11][C:12]1[N:17]=[C:16]([CH3:18])[CH:15]=[CH:14][N:13]=1>CCOCC>[Cl:11][C:12]1[N:17]=[C:16]([CH3:18])[CH:15]=[C:14]([C:2]2[S:1][CH:5]=[CH:4][CH:3]=2)[N:13]=1

Participants

5

Reactant 3

HCID 8030ThiopheneHCID 116296072-Chloro-4-methylpyrimidineHCID 178418339Butyllithium

Product 1

HCID 183237602-Chloro-4-methyl-6-(2-thienyl)pyrimidineYield 12.8%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
0 °C

Procedure

Part B: To thiophene (0.66 g) in dry ether (25 mL) at 0° C. was added n-butyl lithium in hexanes (1.6 M, 2.7 mL) and the reaction was stirred at 0° C. for 15 minutes. After cooling to −30° C., a solution of 2-chloro-4-methylpyrimidine (1.0 g) in ether (10 mL) was slowly added and the reaction was stirred at −30° C. for 30 minutes and at 0° C. an additional 30 minutes before quenching with a mixture of acetic acid (glacial, 0.45 mL), water (0.5 mL) and tetrahydrofuran (1.0 mL). 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (1.77 g) in tetrahydrofuran (5 mL) was added and the reaction mixture was stirred at room temperature for 5 minutes, then cooled to 0° C. before aq. sodium hydroxide solution (3 M, 50 mL) was added. The organic layer was separated, washed with water, and dried with magnesium sulfate. The solvent was evaporated and the resultant crude oil was chromatographed on silica gel (30% ethyl acetate in hexanes; Rf 0.55) to yield 2-chloro-4-methyl-6-(2-thienyl)pyrimidine (0.21 g). Anal. Calcd: % C, 51.46; % H, 3.33; % N, 13.33. Found: % C, 51.77; % H, 3.35; % N, 12.97.

Workup

  1. temperatureAfter cooling to −30° C.
  2. stirringthe reaction was stirred at −30° C. for 30 minutes and at 0° C. an additional 30 minutes
  3. custombefore quenching with a mixture of acetic acid (glacial, 0.45 mL), water (0.5 mL) and tetrahydrofuran (1.0 mL)
  4. addition2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (1.77 g) in tetrahydrofuran (5 mL) was added
  5. stirringthe reaction mixture was stirred at room temperature for 5 minutes
  6. temperaturecooled to 0° C. before aq. sodium hydroxide solution (3 M, 50 mL)
  7. additionwas added
  8. customThe organic layer was separated
  9. washwashed with water
  10. dry with materialdried with magnesium sulfate
  11. customThe solvent was evaporated
  12. customthe resultant crude oil was chromatographed on silica gel (30% ethyl acetate in hexanes; Rf 0.55)

Sources & evidence

ORD record
ord-d78edc0ff1074c38aff01df08c350b5b
Source dataset
uspto-grants-2002_01
Patent number
US06342503B1

Reaction notes

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