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Chlorotrimethylsilane → HCID 86762582, compound

HRID 2401194
Notes
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Reaction equation

HRID 2401194 reaction equation
BrCCBr.C[Si](C)(C)Cl.[C:10]([O:18][CH2:19]I)(=[O:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[Cl:21][C:22]1[CH:27]=[C:26](Cl)[N:25]=[CH:24][N:23]=1>C1COCC1.[Zn].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:10]([O:18][CH2:19][C:26]1[CH:27]=[C:22]([Cl:21])[N:23]=[CH:24][N:25]=1)(=[O:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 78391,2-DibromoethaneHCID 709434,6-DichloropyrimidineHCID 10015543Iodomethyl Benzoate2×

Product 1

HCID 86762582HCID 86762582, compoundYield 22%

Reagents, catalysts & solvents 3

HCID 23994
Zinc
Catalyst
HCID 178418397HCID 178418397, compoundCatalyst
HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
60 °C

Procedure

Zinc (4.81 g, 73.6 mmol) was suspended in THF (6 mL), treated with 1,2-dibromoethane (0.313 mL, 3.63 mmol) and the resulting mixture was heated at 60° C. under argon for 30 minutes. The reaction mixture was allowed to cool to room temperature, treated with trimethylchlorosilane (0.120 mL, 0.938 mmol) and the resulting mixture was stirred at room temperature for 30 minutes. A solution of iodomethyl benzoate (Intermediate 23, 3.15 g, 12.02 mmol) in THF (6 mL) was added and the resulting mixture was stirred at room temperature for 1 hour. This reaction mixture was added to a solution of 4,6-dichloropyrimidine (1.075 g, 7.21 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.695 g, 0.601 mmol) in THF (11 mL) and the resulting mixture was stirred at room temperature under argon for 18 hours. The reaction mixture was filtered through celite, diluted with saturated ammonium chloride solution and extracted with ethyl acetate (×2). The ethyl acetate layers were combined, dried under magnesium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography (Biotage SP4) eluting with a gradient of 0-20% ethyl acetate and isohexane. Product containing fractions were combined and evaporated under reduced pressure to give the title compound as a yellow solid (394 mg);

Workup

  1. temperatureto cool to room temperature
  2. stirringthe resulting mixture was stirred at room temperature for 1 hour
  3. stirringthe resulting mixture was stirred at room temperature under argon for 18 hours
  4. filtrationThe reaction mixture was filtered through celite
  5. additiondiluted with saturated ammonium chloride solution
  6. extractionextracted with ethyl acetate (×2)
  7. customdried under magnesium sulfate
  8. customevaporated under reduced pressure
  9. customThe residue was purified by column chromatography (Biotage SP4)
  10. washeluting with a gradient of 0-20% ethyl acetate and isohexane
  11. additionProduct containing fractions
  12. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-6fe6fad2eb4f48868146112248a078a8
Source dataset
uspto-grants-2014_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08796283B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes