4-Toluenesulfonyl chloride → HCID 11348669, compound

HRID 1596501Notes

Reaction equation

HRID 1596501 reaction equation
[OH:1][C@H:2]([C:5]1[CH:6]=[CH:7][C:8]([NH:11][C:12](=[O:14])[CH3:13])=[N:9][CH:10]=1)[CH2:3][OH:4].[C:15]1([CH3:25])[CH:20]=[CH:19][C:18]([S:21](Cl)(=[O:23])=[O:22])=[CH:17][CH:16]=1>N1C=CC=CC=1>[C:12]([NH:11][C:8]1[N:9]=[CH:10][C:5]([C@@H:2]([OH:1])[CH2:3][O:4][S:21]([C:18]2[CH:19]=[CH:20][C:15]([CH3:25])=[CH:16][CH:17]=2)(=[O:23])=[O:22])=[CH:6][CH:7]=1)(=[O:14])[CH3:13]

Participants

4

Reactant 2

HCID 73974-Toluenesulfonyl chlorideHCID 15477710N-[5-[(1R)-1,2-Dihydroxyethyl]-2-pyridinyl]acetamide

Product 1

HCID 11348669HCID 11348669, compoundYield 80.6%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
5 °C

Procedure

A slurry of (R)-N-(5-(1,2-dihydroxy-ethyl)-pyridin-2-yl)-acetamide (71.2 g, 362 mmol) in anhydrous pyridine (362 ml) was cooled to 5° C. and treated with p-toluenesulfonyl chloride (69.18 g, 362 mmol) in one portion. The reaction mixture was stirred at 5° C. for 20 minutes, then the cooling bath was removed and the mixture was stirred at ambient temperature for two hours. The mixture was then concentrated, dissolved in 30 ml of methanol, concentrated and dissolved in toluene (300 ml) and concentrated again. The residue was treated again with methanol and toluene, then the residue was dissolved in ethyl acetate and washed sequentially with half-saturated brine, brine and dried over sodium sulfate. The filtrate was evaporated to afford 102.2 g (80%) of the title product as light buff crystals. Recrystallization from ethanol-cyclohexane afforded the title product as colorless crystals. mp 124-126° C. 1H NMR (dmso-d6): δ=10.5 (br, 1 H); 8.21 (d, 1 H); 7.94 (d, 1 H); 7.68 (d, 2 H); 7.51 (d of d, 1 H); 7.41 (d, 1 H); 5.87 (d, 1 H); 4.76 (d of d, 1 H); 4.05 (d, 2 H); 2.41 (s, 3 H); 2.10 (s, 3 H). MS (Cl): m/z=351 (M+H+). Optical Rotation: −36.181° (c=1.19, acetone). Analysis: Calculated for C16H18N2O5S: C, 54.85%; H, 5.18%; N, 7.99%. Found: C, 54.91%; H, 5.34%; N, 8.06%.

Workup

  1. customthe cooling bath was removed
  2. stirringthe mixture was stirred at ambient temperature for two hours
  3. concentrationThe mixture was then concentrated
  4. dissolutiondissolved in 30 ml of methanol
  5. concentrationconcentrated
  6. dissolutiondissolved in toluene (300 ml)
  7. concentrationconcentrated again
  8. additionThe residue was treated again with methanol and toluene
  9. dissolutionthe residue was dissolved in ethyl acetate
  10. washwashed sequentially with half-saturated brine, brine
  11. dry with materialdried over sodium sulfate
  12. customThe filtrate was evaporated

Sources & evidence

ORD record
ord-3db7e7410aee494cbb930c69bbc9f60e
Source dataset
uspto-grants-2001_09
Patent number
US06291489B1

Reaction notes

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