Benzyl chloroformate → Benzyl 3-hydroxypyrrolidine-1-carboxylate

HRID 641934Notes

Reaction equation

HRID 641934 reaction equation
Cl.[NH:2]1[CH2:6][CH2:5][CH:4]([OH:7])[CH2:3]1.[OH-].[Na+].Cl[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12]>O>[OH:7][CH:4]1[CH2:5][CH2:6][N:2]([C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:12])[CH2:3]1

Participants

5

Reactant 3

HCID 10387Benzyl chloroformateHCID 14798Sodium HydroxideHCID 27694083-Hydroxypyrrolidine hydrochloride

Product 1

HCID 560953Benzyl 3-hydroxypyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
5 °C

Procedure

Into a 500 mL 3-necked round bottom flask was placed a solution of pyrrolidin-3-ol hydrochloride (20.2 g, 163.43 mmol) in H2O (60 mL) while cooling to 5° C. Adjustment of the pH to 7 was accomplished by the NaOH (10%). This was followed by the addition of a solution of benzyl chloroformate (36.8 g, 216.47 mmol), which was added dropwise with stirring, while cooling to a temperature of 5° C. The resulting solution was allowed to react, with stirring, for 2 hours at 5° C. Then the resulting solution was allowed to react, with stirring, for 1 hour while the temperature was maintained at room temperature. The reaction progress was monitored by TLC (ethyl acetate/petroleum ether=1:2). The resulting solution was extracted three times with 100 mL of ethyl acetate and the organic layers combined and dried over MgSO4 and concentrated by evaporation under vacuum using a rotary evaporator. This resulted in 30 g (crude) of benzyl 3-hydroxypyrrolidine-1-carboxylate as brown oil.

Workup

  1. customInto a 500 mL 3-necked round bottom flask was placed
  2. additionwas added dropwise
  3. customto react
  4. stirringwith stirring, for 2 hours at 5° C
  5. customto react
  6. stirringwith stirring, for 1 hour while the temperature
  7. temperaturewas maintained at room temperature
  8. extractionThe resulting solution was extracted three times with 100 mL of ethyl acetate
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated by evaporation under vacuum
  11. customa rotary evaporator
  12. customThis resulted in 30 g (crude) of benzyl 3-hydroxypyrrolidine-1-carboxylate as brown oil

Sources & evidence

ORD record
ord-256577cbe76e4983870b751478f4f7e8
Source dataset
uspto-grants-2010_04
Patent number
US07696229B2

Reaction notes

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