Triethylamine → cis-1-benzoyl-4-((4-methylsulfonyl)oxy)-L-proline

HRID 1165978Notes

Reaction equation

HRID 1165978 reaction equation
[C:1]([N:9]1[CH2:17][C@@H:16]([OH:18])[CH2:15][C@H:10]1[C:11]([O:13]C)=[O:12])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:26][S:27](Cl)(=[O:29])=[O:28]>ClCCl>[C:1]([N:9]1[CH2:17][C@@H:16]([O:18][S:27]([CH3:26])(=[O:29])=[O:28])[CH2:15][C@H:10]1[C:11]([OH:13])=[O:12])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 1476251(2S,4S)-Methyl 1-benzoyl-4-hydroxypyrrolidine-2-carboxylate

Product 1

HCID 11120569cis-1-benzoyl-4-((4-methylsulfonyl)oxy)-L-prolineYield 61.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (cis)-1-benzoyl-4-hydroxy-L-proline, methyl ester (169.2 g, 0.679 mole) and triethylamine (104.2 ml, 0.747 mole) in dichloromethane (3.3 liters) was cooled to -10° C. under nitrogen and treated dropwise with methanesulfonyl chloride (59.85 ml, 0.74 mole). The reaction was stirred an additional 30 minutes at -5° C. to -10° C. and the volatiles were removed in vacuo. The residue was treated with ethyl acetate and washed with water, 1N HCl, saturated sodium bicarbonate solution, and brine. The organic solution was dried, filtered, and concentrated in vacuo. The residue was dissolved in THF (2.1 liters) and treated with 3.36 N LiOH solution (423 ml) and stirred at room temperature for 1 hour. The THF was removed in vacuo and the aqueous solution was acidified to pH 4. The resulting solid was filtered, washed with ice water, and recrystallized from 95% ethanol-ethyl acetate to afford 130 g of the title compound.

Workup

  1. customthe volatiles were removed in vacuo
  2. additionThe residue was treated with ethyl acetate
  3. washwashed with water, 1N HCl, saturated sodium bicarbonate solution, and brine
  4. customThe organic solution was dried
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in THF (2.1 liters)
  8. additiontreated with 3.36 N LiOH solution (423 ml)
  9. stirringstirred at room temperature for 1 hour
  10. customThe THF was removed in vacuo
  11. filtrationThe resulting solid was filtered
  12. washwashed with ice water
  13. customrecrystallized from 95% ethanol-ethyl acetate

Sources & evidence

ORD record
ord-6fe410b9db1443559ee7cc5f733b3271
Source dataset
uspto-grants-1990_03
Patent number
US04912231

Reaction notes

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