o-Toluenesulfonyl fluoride → HCID 66653956, compound

HRID 571785Notes

Reaction equation

HRID 571785 reaction equation
[CH2:1]([N:8]1[CH2:13][CH:12]([C:14]2[CH:19]=[CH:18][C:17](Br)=[CH:16][CH:15]=2)[O:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]CCCC.[CH3:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[S:33](F)(=[O:35])=[O:34].C([O-])(O)=O.[Na+]>C1COCC1.CCOC(C)=O>[CH2:1]([N:8]1[CH2:9][CH2:10][O:11][CH:12]([C:14]2[CH:19]=[CH:18][C:17]([S:33]([C:28]3[C:27]([CH3:26])=[CH:32][CH:31]=[CH:30][CH:29]=3)(=[O:35])=[O:34])=[CH:16][CH:15]=2)[CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 292589o-Toluenesulfonyl fluorideHCID 516892Sodium BicarbonateHCID 580978794-Benzyl-2-(4-bromo-phenyl)-morpholineHCID 178418339Butyllithium

Product 1

HCID 66653956HCID 66653956, compoundYield 73.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 4-benzyl-6-(4-bromo-phenyl)-morpholine (0.55 g; 1.66 mmol) in THF (25 mL) was added drop wise a solution of n-BuLi in hexanes (1.32 ml; 2.50 mol/1; 3.31 mmol), at −78° C. The resulting mixture was stirred at −78° C., for 30 min. and then 2-methyl-benzenesulfonyl fluoride (0.63 g; 3.64 mmol) was added. After complete addition the mixture was allowed to come to room temperature, and treated with EtOAc and a 5% aqueous NaHCO3-solution. The layers were separated and the organic layer was dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by column chromatography (SiO2, Et2O) to afford 4-benzyl-2-[4-(toluene-2-sulfonyl)-phenyl]-morpholine (0.50 g). The required 2-methyl-benzenesulfonyl fluoride was prepared as follows: To a solution of o-toluenesulfonyl chloride (0.70 mL; 4.85 mmol) in CH3CN (15 mL) was added spray-dried KF (1.13 g; 19.4 mmol). The resulting mixture was stirred at RT for 18 hours, treated with water and extracted with CH2Cl2. The combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo to afford 2-methyl-benzenesulfonyl fluoride (0.68 g).

Workup

  1. customat −78° C
  2. additionAfter complete addition the mixture
  3. customto come to room temperature
  4. customThe layers were separated
  5. dry with materialthe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (SiO2, Et2O)

Sources & evidence

ORD record
ord-ab6ec280626344e18a85333202236293
Source dataset
uspto-grants-2015_05
Patent number
US09029371B2

Reaction notes

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