4-Toluenesulfonyl chloride → HCID 86675112, compound

HRID 404192Notes

Reaction equation

HRID 404192 reaction equation
[F:1][C:2]1[C:3]([CH2:9][OH:10])=[N:4][CH:5]=[C:6]([F:8])[CH:7]=1.[OH-].[K+].[C:13]1([CH3:23])[CH:18]=[CH:17][C:16]([S:19](Cl)(=[O:21])=[O:20])=[CH:15][CH:14]=1>O1CCCC1>[CH3:23][C:13]1[CH:18]=[CH:17][C:16]([S:19]([O:10][CH2:9][C:3]2[C:2]([F:1])=[CH:7][C:6]([F:8])=[CH:5][N:4]=2)(=[O:21])=[O:20])=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 14797Potassium HydroxideHCID 53414314(3,5-Difluoropyridin-2-YL)methanol

Product 1

HCID 86675112HCID 86675112, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (3,5-difluoropyridin-2-yl)methanol (0.25 g, 0.7 mmol) in tetrahydrofuran (THF; 10 mL) was added potassium hydroxide (KOH; 0.14 g, 2.55 mmol) at RT, and the mixture was stirred for 15 min. p-Toluenesulfonyl chloride (0.42 g, 2.21 mmol) was added slowly at RT, and the reaction mixture was stirred for another 18 h. After complete consumption of the starting material (by TLC), the reaction mixture was diluted with H2O (50 mL) and extracted with EtOAc (2×25 mL). The combined organic extracts were washed with H2O (25 mL) and brine (25 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to obtain the crude material. Purification by silica gel column chromatography eluting with 15% EtOAc/hexane afforded compound I-5 (0.18 g, 0.25 mmol, 35%) as colorless liquid. 1H NMR (500 MHz, CDCl3): δ 8.29 (s, 1H), 7.82 (d, J=8.5 Hz, 2H), 7.34 (d, J=8.5 Hz, 2H), 7.20-7.16 (m, 1H), 5.20 (s, 2H), 2.45 (s, 3H)

Workup

  1. additionwas added slowly at RT
  2. customAfter complete consumption of the starting material (by TLC)
  3. additionthe reaction mixture was diluted with H2O (50 mL)
  4. extractionextracted with EtOAc (2×25 mL)
  5. washThe combined organic extracts were washed with H2O (25 mL) and brine (25 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c591122e9f4a4b728f619ebae5fb570e
Source dataset
uspto-grants-2014_06
Patent number
US08748461B2

Reaction notes

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