4-Toluenesulfonyl chloride → 1,1-Dimethylethyl (3S)-3-[(3-chloro-4-cyanophenyl)amino]-4-{[(4-methylphenyl)sulfonyl]oxy}butanoate

HRID 1160391Notes

Reaction equation

HRID 1160391 reaction equation
[C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[Cl:12][C:13]1[CH:14]=[C:15]([NH:21][C@H:22]([CH2:31][OH:32])[CH2:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH:16]=[CH:17][C:18]=1[C:19]#[N:20]>N1C=CC=CC=1>[Cl:12][C:13]1[CH:14]=[C:15]([NH:21][C@H:22]([CH2:31][O:32][S:7]([C:4]2[CH:5]=[CH:6][C:1]([CH3:11])=[CH:2][CH:3]=2)(=[O:9])=[O:8])[CH2:23][C:24]([O:26][C:27]([CH3:29])([CH3:28])[CH3:30])=[O:25])[CH:16]=[CH:17][C:18]=1[C:19]#[N:20]

Participants

4

Reactant 2

HCID 73974-Toluenesulfonyl chlorideHCID 595162281,1-Dimethylethyl (3S)-3-[(3-chloro-4-cyanophenyl)amino]-4-hydroxybutanoate

Product 1

HCID 866183601,1-Dimethylethyl (3S)-3-[(3-chloro-4-cyanophenyl)amino]-4-{[(4-methylphenyl)sulfonyl]oxy}butanoateYield 87%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

p-Toluenesulfonyl chloride (18.2 g, 96 mmol) was added portion-wise to an ice cold solution of 1,1-dimethylethyl (3S)-3-[(3-chloro-4-cyanophenyl)amino]-4-hydroxybutanoate (27.0 g, 87 mmol) in pyridine (75 mL). After stirring at 0° C. for 15 min, ice bath was removed and the reaction was stirred at room temperature for 2.5 h. The reaction was poured into stirred, ice/H2O (400 mL). When the product solidified, it was filtered, and the solid washed well with H2O. The solid was dissolved in EtOAc (350 mL), and washed successively with H2O, aq. citric acid, and H2O. The EtOAc solution was treated with charcoal, dried (MgSO4), filtered, and the solvent evaporated. The crude product was triturated with a mixture of Et2O (150 mL) and petroleum ether (50 mL) to afford the pure product (35.0 g, 87%). 1H-NMR (CDCl3) δ: 1.42 (9H, s), 2.47 (3H, s), 2.60 (2H, m), 4.04 (1H, m), 4.22 (2H, m), 6.45 (1H, dd, J=8 Hz, 4 Hz), 6.56 (1H, d, J=2.4 Hz), 7.35 (3H, m), 7.75 (2H, d, J=8.4 Hz). LC-MS (ES) m/e 465.3 (M+H)+.

Workup

  1. customice bath was removed
  2. stirringthe reaction was stirred at room temperature for 2.5 h
  3. additionThe reaction was poured
  4. stirringinto stirred
  5. filtrationit was filtered
  6. washthe solid washed well with H2O
  7. dissolutionThe solid was dissolved in EtOAc (350 mL)
  8. washwashed successively with H2O, aq. citric acid, and H2O
  9. additionThe EtOAc solution was treated with charcoal
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. customthe solvent evaporated
  13. customThe crude product was triturated with a mixture of Et2O (150 mL) and petroleum ether (50 mL)

Sources & evidence

ORD record
ord-53fcbf1403e64823a5a5ea5f21372a86
Source dataset
uspto-grants-2010_10
Patent number
US07816395B2

Reaction notes

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