Sodium Carbonate → 2-Chloro-4-(7-chlorobenzo[b]thiophen-2-yl)pyrimidine

HRID 1986249Notes

Reaction equation

HRID 1986249 reaction equation
[Cl:1][C:2]1[C:7]2[S:8][CH:9]=[CH:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.B(OC(C)C)(OC(C)C)OC(C)C.C([Li])CCC.[Cl:29][C:30]1[N:35]=[C:34](Cl)[CH:33]=[CH:32][N:31]=1.C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:29][C:30]1[N:35]=[C:34]([C:9]2[S:8][C:7]3[C:2]([Cl:1])=[CH:3][CH:4]=[CH:5][C:6]=3[CH:10]=2)[CH:33]=[CH:32][N:31]=1

Participants

9

Reactant 5

HCID 10340Sodium CarbonateHCID 21531Triisopropyl borateHCID 775312,4-DichloropyrimidineHCID 110628127-Chloro-1-benzothiopheneHCID 178418339Butyllithium

Product 1

HCID 866253732-Chloro-4-(7-chlorobenzo[b]thiophen-2-yl)pyrimidineYield 42%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-75 °C

Procedure

A solution of 7-chlorobenzo[b]thiophene (10.0 g, 59.3 mmol) in THF (100 mL) is cooled to −70° C. and triisopropyl borate (12.3 g, 65.2 mmol) is added. n-Butyl lithium (n-BuLi) (40.8 mL, 40.8 mmol, 1.6 M in hexane) is added dropwise via syringe over 40 minutes. After stirring 10 minutes at −75° C., the cold bath is removed and the mixture is allowed to warm to room temperature over 30 minutes. After 3 hours, to the mixture is added 2,4-dichloropyrimidine (8.83 g, 59.3 mmol), 2M Na2CO3 (60 mL, 120 mmol), 1,1′-bis(diphenylphosphino)ferrocene (1.64 g, 2.96 mmol) and palladium acetate (666 mg, 2.96 mmol) and the mixture is heated to reflux for 18 hours. The cooled mixture is concentrated under reduced pressure, extracted from water with 10% MeOH/CHCl3 (2×200 mL) and concentrated under reduced pressure. The crude material is subjected to chromatography on silica gel eluting with dichloromethane in hexanes 0-100%, to provide the title compound as a light yellow solid (6.95 g, 42% yield).

Workup

  1. customthe cold bath is removed
  2. temperatureto warm to room temperature over 30 minutes
  3. waitAfter 3 hours
  4. temperaturethe mixture is heated
  5. temperatureto reflux for 18 hours
  6. concentrationThe cooled mixture is concentrated under reduced pressure
  7. extractionextracted from water with 10% MeOH/CHCl3 (2×200 mL)
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c4ff34e9bf0a4198966150b1821d85d1
Source dataset
uspto-grants-2009_06
Patent number
US07547691B2

Reaction notes

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