2,4,6-Trimethylphenol → 2-Chloro-4-(mesityloxy)thieno[2,3-d]pyrimidine

HRID 736316Notes

Reaction equation

HRID 736316 reaction equation
[H-].[Na+].[CH3:3][C:4]1[CH:9]=[C:8]([CH3:10])[CH:7]=[C:6]([CH3:11])[C:5]=1[OH:12].[Cl:13][C:14]1[N:15]=[C:16](Cl)[C:17]2[CH:22]=[CH:21][S:20][C:18]=2[N:19]=1>C1COCC1.O>[Cl:13][C:14]1[N:15]=[C:16]([O:12][C:5]2[C:6]([CH3:11])=[CH:7][C:8]([CH3:10])=[CH:9][C:4]=2[CH3:3])[C:17]2[CH:22]=[CH:21][S:20][C:18]=2[N:19]=1

Participants

6

Reactant 3

HCID 106982,4,6-TrimethylphenolHCID 24758Sodium hydrideHCID 122173242,4-Dichlorothieno[2,3-d]pyrimidine

Product 1

HCID 578488772-Chloro-4-(mesityloxy)thieno[2,3-d]pyrimidineYield 97.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A stirred suspension of NaH (9.5 mg, 0.24 mmol) in dry THF (1 mL) was added 2,4,6-trimethyl phenol (32.1 mg, 0.24 mmol) and stirred at room temperature for 30 min under Argon. The reaction mixture was added to a solution of 2,4-dichlorothieno[2,3-d]pyrimidine (48.1 mg, 0.24 mmol) in dry THF (1.5 mL) at 0° C. and allow it to slowly warmed up to room temperature. After stirring the reaction for 4 h, the resulting mixture was diluted with water and washed with EtOAc. The combined organic layers were washed with water, brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by column chromatography, eluting with hexanes/ethyl acetate (9:1) to give the product as a white solid (71 mg, 97%):

Workup

  1. temperatureto slowly warmed up to room temperature
  2. stirringAfter stirring
  3. customthe reaction for 4 h
  4. washwashed with EtOAc
  5. washThe combined organic layers were washed with water, brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by column chromatography
  10. washeluting with hexanes/ethyl acetate (9:1)

Sources & evidence

ORD record
ord-48842ee22dfe41f58839d6f4ce79cbb3
Source dataset
uspto-grants-2009_09
Patent number
US07595324B2

Reaction notes

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