Ammonium Chloride → HCID 86702158, compound

HRID 1776236Notes

Reaction equation

HRID 1776236 reaction equation
[CH3:1][O:2][C:3]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:4]=1[CH2:5][N:6]1[CH2:10][CH2:9][CH:8]([F:11])[S:7]1(=[O:13])=[O:12].C([Li])CCC.[F:25]NS(C1C=CC=CC=1)(=O)=O.[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:4]=1[CH2:5][N:6]1[CH2:10][CH2:9][C:8]([F:25])([F:11])[S:7]1(=[O:13])=[O:12]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 15373214N-FluorobenzenesulfonamideHCID 86702159HCID 86702159, compoundHCID 178418339Butyllithium

Product 1

HCID 86702158HCID 86702158, compoundYield 2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(2,4-dimethoxybenzyl)-5-fluoroisothiazolidine-1,1-dioxide (5.700 g, 19.7 mmol) in anhydrous tetrahydrofuran (225 mL), cooled to −78° C., was slowly added n-butyl lithium (14.973 mL of a 2.5 N solution in hexanes, 37.4 mmol) and the resulting dark orange/red solution stirred for 1 hr. A solution of N-fluorobenzene sulfonamide (14.6 g, 46.3 mmol) in anhydrous tetrahydrofuran (60 mL) was added slowly over 30 mins, stirring at −78° C. for 3 hrs and at room temperature for 2.5 hrs. The reaction was poured into saturated aqueous ammonium chloride, diluted with ethyl acetate, and the organic layer isolated. The organic layer was washed with saturated aqueous sodium chloride, dried (anhydrous sodium sulfate), filtered, and concentrated in vacuo. The crude material was suspended in methylene chloride and filtered through a pad of silica gel, washing with methylene chloride, and concentrating the solution. The crude material was purified by silica gel chromatography (20-75% ethyl acetate/hexanes) and then by preparative HPLC (C18, 32-95% acetonitrile/water over 17 mins) to give a tan oil (0.106 g, 2%). 1H NMR (CDCl3, 300 MHz) δ 7.21-7.18 (d, 1H, J=8.4 Hz), 6.49-6.45 (m, 2H), 4.28 (s, 2H), 3.82 (s, 3H), 3.14 (s, 3H), 3.19-3.15 (m, 2H), 2.70-2.55 (m, 2H).

Workup

  1. stirringstirring at −78° C. for 3 hrs and at room temperature for 2.5 hrs
  2. customthe organic layer isolated
  3. washThe organic layer was washed with saturated aqueous sodium chloride
  4. dry with materialdried (anhydrous sodium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. filtrationfiltered through a pad of silica gel
  8. washwashing with methylene chloride
  9. concentrationconcentrating the solution
  10. customThe crude material was purified by silica gel chromatography (20-75% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-9d0e25314880403592ecc3e849106fee
Source dataset
uspto-grants-2016_02
Patent number
US09265772B2

Reaction notes

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