1-Iodohexane → HCID 67401054, Verbindung

Temperatur

70 °C

To a solution of 4-hydroxy-piperidine (190 mg, 1.88 mmol) and DIEA (0.87 mL, 5.13 mmol) in 10 mL CH2Cl2 was added a solution of 5-({[1-(4-Chloro-phenyl)-methanoyl]-amino}-methyl)-thiophene-2-sulfonyl chloride 1b (500 mg, 1.71 mmol) in hot DCE. The reaction mixture was stirred for 4 h. 100 mL EtOAc were added and excess of amines were removed by extraction with HCl (1N). The sulfonamide intermediate was used without any further purification, where 300 mg (0.84 mmol) were dissolved in dry DMF under Ar. NaH (60 mg, 50% in parafine oil, 1.01 mmol) were added as a solid. The colour of the reaction changed to orange. The reaction mixture was stirred for 15′ until no gas evolution was observed anymore. Iodohexane (356 mg, 1.68 mmol) dissolved in 1 mL DMF was added to the above solution and the reaction mixture was heated at 70° C. overnight. DMF was evaporated to dryness and the crude was taken up in CH2Cl2. The organic layer was washed twice with water, dried over MgSO4 and evaporated to dryness. The crude was purified on silica gel using cyclohexane/EtOAc 3:1 as eluent to obtain 210 mg (59%) of pure 326a as a colorless oil.

1. customwere removed by extraction with HCl (1N)
2. customThe sulfonamide intermediate was used without any further purification, where 300 mg (0.84 mmol)
3. dissolutionwere dissolved in dry DMF under Ar
4. stirringThe reaction mixture was stirred for 15′ until no gas evolution
5. additionwas added to the above solution
6. customDMF was evaporated to dryness
7. washThe organic layer was washed twice with water
8. dry with materialdried over MgSO4
9. customevaporated to dryness
10. customThe crude was purified on silica gel

ORD-Eintrag

ord-5f5d8992766e4071981ca8bd53312e04

Quelldatensatz

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08012995B1