1-Iodohexane → HCID 67401054, compound

HRID 906640Notes

Reaction equation

HRID 906640 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.CCN(C(C)C)[CH:11]([CH3:13])[CH3:12].ClC1C=[CH:22][C:21]([C:24]([NH:26][CH2:27][C:28]2[S:32][C:31]([S:33](Cl)(=[O:35])=[O:34])=[CH:30][CH:29]=2)=O)=CC=1.[H-].[Na+].I[CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH3:45]>C(Cl)Cl.ClCCCl.CN(C=O)C.CCOC(C)=O>[CH2:13]([N:26]([CH2:24][CH:21]=[CH2:22])[CH2:27][C:28]1[S:32][C:31]([S:33]([N:5]2[CH2:6][CH2:7][CH:2]([O:1][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH3:45])[CH2:3][CH2:4]2)(=[O:34])=[O:35])=[CH:30][CH:29]=1)[CH:11]=[CH2:12]

Participants

10

Reactant 5

HCID 125271-IodohexaneHCID 24758Sodium hydrideHCID 79341Piperidin-4-olHCID 81531DiisopropylethylamineHCID 27357135-((4-Chlorobenzamido)methyl)thiophene-2-sulfonyl chloride

Product 1

HCID 67401054HCID 67401054, compound

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-5f5d8992766e4071981ca8bd53312e04
Source dataset
uspto-grants-2011_09
Patent number
US08012995B1

Reaction notes

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