4-Methylbenzenethiol → 4-(5-Methyl-4-(tosylmethyl)oxazol-2-yl)-N-(pyridin-3-ylmethyl)benzamide

HRID 931457Notes

Reaction equation

HRID 931457 reaction equation
O[CH2:2][C:3]1[N:4]=[C:5]([C:9]2[CH:24]=[CH:23][C:12]([C:13]([NH:15][CH2:16][C:17]3[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=3)=[O:14])=[CH:11][CH:10]=2)[O:6][C:7]=1[CH3:8].CCN(CC)CC.[CH3:32][S:33](Cl)(=[O:35])=[O:34].C([O-])([O-])=O.[K+].[K+].[CH3:43][C:44]1[CH:49]=[CH:48]C(S)=[CH:46][CH:45]=1.OOS([O-])=O.[K+]>CN(C=O)C.O.CO>[CH3:8][C:7]1[O:6][C:5]([C:9]2[CH:24]=[CH:23][C:12]([C:13]([NH:15][CH2:16][C:17]3[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=3)=[O:14])=[CH:11][CH:10]=2)=[N:4][C:3]=1[CH2:2][S:33]([C:32]1[CH:48]=[CH:49][C:44]([CH3:43])=[CH:45][CH:46]=1)(=[O:35])=[O:34]

Participants

10

Reactant 6

HCID 78114-MethylbenzenethiolHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 23707502Potassium hydroxy sulfiteHCID 898555574-[4-(Hydroxymethyl)-5-methyl-1,3-oxazol-2-yl]-N-(3-pyridinylmethyl)benzamide

Product 1

HCID 209169374-(5-Methyl-4-(tosylmethyl)oxazol-2-yl)-N-(pyridin-3-ylmethyl)benzamideYield 28.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of alcohol 56 (163 mg, 0.5 mmol) in anhydrous DMF (7 mL) was cooled to 0° C. NEt3 (0.14 mL, 1 mmol) and MsCl (47 λL, 0.6 mmol) were added successively and the reaction mixture was stirred at 0° C. for 1 h. K2CO3 (138 mg, 1 mmol) and 4-methylthiophenol (68 mg, 0.55 mmol) were added and the reaction mixture was stirred at 60° C. for 1 h. The reaction mixture was then cooled to 20° C. and partitioned between EtOAc (200 mL) and H2O (50 mL). The organic fraction was washed with H2O (2×50 mL), washed with brine (50 mL), and dried. The solvent was evaporated to give the crude sulfide (158 mg, 0.37 mmol) which was used without further purification. A solution of Oxone® (172 mg, 0.28 mmol) in H2O (3 mL) was added at 0° C. to a stirred solution of crude sulfide (88 mg, 0.2 mmol) in MeOH (3 mL), and the reaction mixture was stirred for 1 h at 20° C. H2O was added (50 mL), the mixture was extracted with DCM (3×50 mL) and the organic phase was washed with brine (50 mL), dried, and the solvent was evaporated. Remaining sulfide (70 mg, 0.16 mmol) was treated as described and the combined crude products were purified by column chromatography, eluting with 5% MeOH/EtOAc, to give sulfone 9 (65 mg, 28%) as a white powder: spectroscopically identical to the sample prepared above.

Workup

  1. stirringthe reaction mixture was stirred at 60° C. for 1 h
  2. temperatureThe reaction mixture was then cooled to 20° C.
  3. custompartitioned between EtOAc (200 mL) and H2O (50 mL)
  4. washThe organic fraction was washed with H2O (2×50 mL)
  5. washwashed with brine (50 mL)
  6. customdried
  7. customThe solvent was evaporated
  8. customto give the crude sulfide (158 mg, 0.37 mmol) which
  9. customwas used without further purification
  10. stirringthe reaction mixture was stirred for 1 h at 20° C
  11. extractionthe mixture was extracted with DCM (3×50 mL)
  12. washthe organic phase was washed with brine (50 mL)
  13. customdried
  14. customthe solvent was evaporated
  15. customthe combined crude products were purified by column chromatography
  16. washeluting with 5% MeOH/EtOAc

Sources & evidence

ORD record
ord-05d59f63765c4ba1b7a3d047cea4017a
Source dataset
uspto-grants-2016_03
Patent number
US09296732B2

Reaction notes

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