1-(4-Methylbenzenesulfonyl)aziridine → [3-(4-Chloro-benzenesulfonyl)-3-(2,3,6-trifluoro-phenyl)-propyl]-4-methyl-benzenesulfonamide

HRID 564342

Reaction equation

HRID 564342 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH2:11][C:12]2[C:17]([F:18])=[C:16]([F:19])[CH:15]=[CH:14][C:13]=2[F:20])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[Li][CH2:22][CH2:23][CH2:24][CH3:25].[C:26]1(C)[CH:31]=C[C:29]([S:32]([N:35]2CC2)(=[O:34])=[O:33])=[CH:28][CH:27]=1>C1COCC1.CN(CCN(C)C)C.C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([CH:11]([C:12]2[C:13]([F:20])=[CH:14][CH:15]=[C:16]([F:19])[C:17]=2[F:18])[CH2:25][CH2:24][C:23]2[CH:22]=[C:26]([CH3:31])[CH:27]=[CH:28][C:29]=2[S:32]([NH2:35])(=[O:34])=[O:33])(=[O:10])=[O:9])=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 5612741-(4-Methylbenzenesulfonyl)aziridineHCID 589503342-(4-Chloro-benzenesulfonylmethyl)-1,3,4-trifluoro-benzeneHCID 178418339Butyllithium

Product 1

HCID 131729296[3-(4-Chloro-benzenesulfonyl)-3-(2,3,6-trifluoro-phenyl)-propyl]-4-methyl-benzenesulfonamideYield 54.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 86588997Thf tmedaSolvent

Procedure

A solution of 2-(4-chloro-benzenesulfonylmethyl)-1,3,4-trifluoro-benzene (5.6 g, 17.5 mmol) in THF/TMEDA (5:1, 180 mL) at −78° C. was treated with n-BuLi (12 mL, 17.5 mmol, 1.5 M in hexanes). After 15 min, a solution of N-p-toluenesulfonyl aziridine (3.5 g, 17.5 mmol, prepared as described in Eur. J. Org. Chem. 2002, 3004) in THF (10 mL) was added, and the reaction mixture warmed slowly to ambient temperature. After 4 h, the reaction mixture was quenched with 1N HCl and extracted with EtOAc (2×). The combined organic extracts were washed with saturated aqueous NaHCO3, brine, dried over MgSO4 and concentrated in vacuo. Flash chromatography (25→50% EtOAc/Hex) provided the title compound (4.9 g, 54%): 1H NMR (CDCl3 400 MHz) δ 7.64 (d, J=8.1 Hz, 2H), 7.57 (d, J=8.1 Hz, 2H), 7.43 (d, J=8.1 Hz, 2H), 7.28 (d, J=8.1 Hz, 2H), 7.14 (m, 1H), 6.75 (m, 1H), 4.81 (m, 1H), 3.17 (ddd, J=7.1, 7.1, 5.6 Hz, 1H), 2.96 (m, 1H), 2.64 (m, 1H), 2.47 (m, 1H), 2.41 (s, 3H).

Workup

  1. waitAfter 4 h
  2. customthe reaction mixture was quenched with 1N HCl
  3. extractionextracted with EtOAc (2×)
  4. washThe combined organic extracts were washed with saturated aqueous NaHCO3, brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-631d4db9398848089264d4ee1eeb1764
Source dataset
uspto-grants-2011_11
Patent number
US08067621B2

Linked notes

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