Hydrochloric Acid → 1-(1-methyl-1H-imidazol-4-ylsulfonyl)azetidine-3-carbonitrile

HRID 221204Notes

Reaction equation

HRID 221204 reaction equation
C([N:8]1[CH2:11][CH:10]([C:12]#[N:13])[CH2:9]1)(OC(C)(C)C)=O.Cl.CCN(C(C)C)C(C)C.[CH3:24][N:25]1[CH:29]=[C:28]([S:30](Cl)(=[O:32])=[O:31])[N:27]=[CH:26]1>O1CCOCC1>[CH3:24][N:25]1[CH:29]=[C:28]([S:30]([N:8]2[CH2:9][CH:10]([C:12]#[N:13])[CH2:11]2)(=[O:32])=[O:31])[N:27]=[CH:26]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 27368871-methyl-1H-imidazole-4-sulfonyl chlorideHCID 106312831-Boc-3-cyanoazetidine

Product 1

HCID 595344921-(1-methyl-1H-imidazol-4-ylsulfonyl)azetidine-3-carbonitrileYield 80%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of 1-N-Boc-3-cyanoazetidine (5.0 g, 27.5 mmol) in 1,4-dioxane (50 mL) was added 4 N HCl (50 mL) and stirred for 2 h. The reaction was concentrated under vacuum. The residue was dissolved in CH2Cl2 (60 mL) and DIPEA (10.6 mL, 60.4 mmol) and added 1-methylimidazole-4-sulfonyl chloride (4.94 g, 27.5 mmol) and stirred at room temperature for 20 h. The reaction mixture was washed with 2 N NaOH (50 mL), dried over MgSO4 and concentrated under vacuum to afford 8 as a white crystalline solid (4.97 g, 80%); 1H-nmr (300 MHz, CDCl3) δ 7.06 (s, 1H), 7.56 (s, 1H), 4.27-4.19 (m, 4H), 3.82 (s, 3H), 3.43-3.31 (m, 1H); LC-MS (214) 99%, 0.93 min, m/z 227.1 (M+H).

Workup

  1. concentrationThe reaction was concentrated under vacuum
  2. dissolutionThe residue was dissolved in CH2Cl2 (60 mL)
  3. stirringstirred at room temperature for 20 h
  4. washThe reaction mixture was washed with 2 N NaOH (50 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-813792d6910d47c09ead3188c7288b7d
Source dataset
uspto-grants-2012_06
Patent number
US08207155B2

Reaction notes

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