Sodium Iodide → HCID 23499475, compound

HRID 1836342Notes

Reaction equation

HRID 1836342 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][N:11]1[CH2:16][CH2:15][CH:14]([S:17]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26]O)=[CH:22][CH:21]=2)(=[O:19])=[O:18])[CH2:13][CH2:12]1.CCN(CC)CC.CS(Cl)(=O)=O.[Na+].[I-].C([O-])([O-])=O.[Cs+].[Cs+].[NH:48]1[CH:52]=[N:51][N:50]=[N:49]1>C1COCC1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][N:11]1[CH2:16][CH2:15][CH:14]([S:17]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][N:48]3[CH:52]=[N:51][N:50]=[N:49]3)=[CH:22][CH:21]=2)(=[O:19])=[O:18])[CH2:13][CH2:12]1

Participants

8

Reactant 6

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 10796Cesium carbonateHCID 31297Methanesulfonyl chlorideHCID 23499479HCID 23499479, compoundHCID 178418441HCID 178418441, compound

Product 1

HCID 23499475HCID 23499475, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1-[2-(2,4-Difluorophenyl)ethyl]-4-(4-hydroxymethylphenylsulphonyl)piperidine (0.20 g, 0.51 mmol) was dissolved in anhydrous THF (10 ml) under nitrogen at 0° C. Et3N (0.14 ml, 1 mmol) and methanesulphonyl chloride (0.078 ml, 1 mmol) were added dropwise. The mixture was stirred at room temperature for 1 h, quenched with water and extracted into EtOAc. The organic extracts were combined, washed with water, dried (MgSO4) and solvent evaporated. The residue was dissolved in IPA (20 ml), and heated to reflux overnight with NaI (0.076 g), Cs2CO3 (0.197 g) and 1H-tetrazole (1.06 g, 15 mmol). The reaction mixture was cooled to room temperature and concentrated. The residue was partitioned between water and CH2Cl2 and the organic layer was washed with water, dried (MgSO4) and concentrated. Purification by column chromatography (SiO2; EtOAc:pet. ether 60-80° 1:1 to EtOAc:MeOH 99:1) gave the title compound, m.p. 168-169° C. (Found: C, 56.00; H, 4.91; N, 15.82. C21H23N5O2SF2 requires C, 56.36; H, 5.18; N, 15.63). δH (360 MHz, CDCl3) 1.64-1.77 (2H, m), 1.97-2.05 (4H, m), 2.48-2.53 (2H, m), 2.70-2.76 (2H, m), 2.86-2.95 (1H, m), 3.01-3.10 (2H, m), 5.71 (2H, s), 6.72-6.80 (2H, m), 7.08-7.15 (1H, m), 7.46 (2H, d, J 8 Hz), 7.91 (2H, d, J 8 Hz), 8.65 (1H, s).

Workup

  1. customquenched with water
  2. extractionextracted into EtOAc
  3. washwashed with water
  4. dry with materialdried (MgSO4) and solvent
  5. customevaporated
  6. dissolutionThe residue was dissolved in IPA (20 ml)
  7. temperatureheated
  8. temperatureThe reaction mixture was cooled to room temperature
  9. concentrationconcentrated
  10. customThe residue was partitioned between water and CH2Cl2
  11. washthe organic layer was washed with water
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated
  14. customPurification by column chromatography (SiO2; EtOAc:pet. ether 60-80° 1:1 to EtOAc:MeOH 99:1)

Sources & evidence

ORD record
ord-f909ead4462d448db8e12900483d557c
Source dataset
uspto-grants-2004_08
Patent number
US06777430B2

Reaction notes

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