Trimethyl orthoformate → HCID 90303529, compound

HRID 1051931Notes

Reaction equation

HRID 1051931 reaction equation
[Br:1][C:2]1[S:6][CH:5]=[N:4][C:3]=1[O:7][CH2:8][CH:9]1[CH2:13][O:12]C(C)(C)O1.CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1.C(OC)(OC)OC.C(Br)(C)=O.C([O-])([O-])=O.[K+].[K+]>CO.C(Cl)Cl>[Br:1][C:2]1[S:6][CH:5]=[N:4][C:3]=1[O:7][CH2:8][CH:9]1[CH2:13][O:12]1

Participants

8

Reactant 5

HCID 9005Trimethyl orthoformate2×HCID 10482Acetyl bromideHCID 11430Potassium CarbonateHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)2×HCID 90303406HCID 90303406, compound

Product 1

HCID 90303529HCID 90303529, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent3×HCID 6344DichloromethaneSolvent2×

Procedure

A soln. of 5-bromo-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)thiazole (18.80 g, 63.9 mmol) and PPTS (0.80 g, 3.19 mmol) in MeOH (256 mL) was stirred under reflux for 3 h. More PPTS (0.40 g, 1.60 mmol) was added and the mixture was stirred under reflux for additional 2 h. The mixture was conc. in vacuo, the residue was dissolved in MeOH (256 mL) and stirred under reflux for 2 h. The mixture was conc. in vacuo, the residue was dissolved in DCM (256 mL) and treated with trimethyl orthoformate (10.5 mL, 95.8 mmol). The mixture was stirred overnight at RT. Subsequently, additional trimethyl orthoformate (3.5 mL, 31.9 mmol) was added and the mixture was stirred at RT for 1 h. Then, the mixture was conc. in vacuo, the residue was dissolved in DCM (256 mL), treated with AcBr (5.73 mL, 76.7 mmol) and stirred at RT for 90 min. Subsequently, the mixture was conc. in vacuo, the residue was dissolved in MeOH (320 mL) and K2CO3 (17.66 g, 128 mmol) was added to the mixture. After the mixture was stirred at RT for 90 min, the mixture was filtrated and the filtrate was poured into cold aq. sat. NH4Cl. The mixture was extracted with EtOAc, the comb. org. layers were washed with brine, dried over MgSO4, and conc. in vacuo. The residue was purified by means of CC (2-40% EtOAc/Hept) to provide a yellow oil.

Workup

  1. temperatureunder reflux for 3 h
  2. temperatureunder reflux for additional 2 h
  3. stirringstirred
  4. temperatureunder reflux for 2 h
  5. stirringThe mixture was stirred overnight at RT
  6. stirringthe mixture was stirred at RT for 1 h
  7. stirringstirred at RT for 90 min
  8. stirringAfter the mixture was stirred at RT for 90 min
  9. filtrationthe mixture was filtrated
  10. additionthe filtrate was poured into cold aq. sat. NH4Cl
  11. extractionThe mixture was extracted with EtOAc
  12. washlayers were washed with brine
  13. dry with materialdried over MgSO4
  14. customThe residue was purified by means of CC (2-40% EtOAc/Hept)
  15. customto provide a yellow oil

Sources & evidence

ORD record
ord-4d6bc8525ba241f3b2875bb9cee8f3d5
Source dataset
uspto-grants-2016_07
Patent number
US09388197B2

Reaction notes

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