L-Hydroxyproline → HCID 391526, compound

HRID 2291127Notes

Reaction equation

HRID 2291127 reaction equation
[OH:1][C@H:2]1[CH2:6][NH:5][C@H:4]([C:7]([OH:9])=[O:8])[CH2:3]1.[OH-].[Na+].[C:12]1([CH3:22])[CH:17]=[CH:16][C:15]([S:18](Cl)(=[O:20])=[O:19])=[CH:14][CH:13]=1>C(OCC)C>[OH:1][C@H:2]1[CH2:6][N:5]([S:18]([C:15]2[CH:16]=[CH:17][C:12]([CH3:22])=[CH:13][CH:14]=2)(=[O:20])=[O:19])[C@H:4]([C:7]([OH:9])=[O:8])[CH2:3]1

Participants

5

Reactant 3

HCID 5810L-HydroxyprolineHCID 73974-Toluenesulfonyl chlorideHCID 14798Sodium Hydroxide

Product 1

HCID 391526HCID 391526, compoundYield 90.1%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

35.6 g (0.27 mol) of (2S,4R)-4-hydroxyproline were dissolved in 300 ml (0.60 mol) of 2N sodium hydroxide in a 750 ml sulphonation flask which was provided with stirrer, dropping funnel, thermometer and condenser. Thereupon, within 10 minutes there was added dropwise thereto a solution of 63 g (0.33 mol) of p-toluenesulphonyl chloride in 180 ml of diethyl ether. The temperature was held at 16°-20° C. by means of a water bath. After intensive stirring at room temperature for 16 hours, the reaction has finished. The aqueous phase (pH about 7) was separated and back-washed with 250 ml of diethyl ether. The ether phases were back-washed a further twice with 100 ml of deionized water each time. The combined aqueous phases were acidified to pH 2 with 25 ml of concentrated hydrochloric acid (27%) while cooling with ice at 5° C. and stirred for 1.5 hours at 5° C. The separated crystals were filtered off under suction, washed with 1 liter of deionized water and dried for 16 hours in a vacuum drying oven at 40° C./17 mbar. The resulting product (76.2 g of white crystals of melting point 142°-145° C.) was, for purification, dissolved in 200 ml of hot ethanol/water (1:4, v/v) and recrystallized while stirring and slowly cooling to 5° C. The white crystals obtained after drying (73.4 g) were again recrystallized from 150 ml of ethanol/water (1:4, v/v) as previously described and dried in a vacuum drying oven at 50° C./17 mbar. There were obtained 69.4 g (89.6%) of (2S,4R)-4-hydroxy-1-(p-tolylsulphonyl)-2-pyrrolidinecarboxylic acid of melting point 146°-147° C.; [α]D20 =-87.6° (c=1 in ethanol).

Workup

  1. customwas provided with stirrer
  2. additionThereupon, within 10 minutes there was added dropwise
  3. customThe temperature was held at 16°-20° C. by means of a water bath
  4. customThe aqueous phase (pH about 7) was separated
  5. washback-washed with 250 ml of diethyl ether
  6. washThe ether phases were back-washed a further twice with 100 ml of deionized water each time
  7. temperaturewhile cooling with ice at 5° C.
  8. stirringstirred for 1.5 hours at 5° C
  9. filtrationThe separated crystals were filtered off under suction
  10. washwashed with 1 liter of deionized water
  11. customdried for 16 hours in a vacuum
  12. customdrying oven at 40° C./17 mbar
  13. customThe resulting product (76.2 g of white crystals of melting point 142°-145° C.) was, for purification
  14. dissolutiondissolved in 200 ml of hot ethanol/water (1:4, v/v)
  15. customrecrystallized
  16. stirringwhile stirring
  17. temperatureslowly cooling to 5° C
  18. customThe white crystals obtained
  19. customafter drying (73.4 g)
  20. customwere again recrystallized from 150 ml of ethanol/water (1:4, v/v)
  21. customdried in a vacuum
  22. customdrying oven at 50° C./17 mbar

Sources & evidence

ORD record
ord-f088e43b66c34a8a83680efa2fcab796
Source dataset
uspto-grants-1986_10
Patent number
US04620013

Reaction notes

Loading…