Benzyl chloroformate → (R)-(-)-1-CBZ-3-pyrrolidinol

HRID 1601719Notes

Reaction equation

HRID 1601719 reaction equation
Cl.[OH:2][C@H:3]1[CH2:7][CH2:6][NH:5][CH2:4]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:2][C@@H:3]1[CH2:7][CH2:6][N:5]([C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:12])[CH2:4]1

Participants

5

Reactant 3

HCID 10387Benzyl chloroformateHCID 14798Sodium Hydroxide2×HCID 22309122(S)-3-Hydroxypyrrolidine hydrochloride

Product 1

HCID 11183628(R)-(-)-1-CBZ-3-pyrrolidinol

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

The pH of a solution of 6.18 g of (S)-3-hydroxy-pyrrolidine hydrochloride in 175 ml of water was adjusted to 10 with 10% sodium hydroxide solution and cooled to 0°-5° C. 7.1 ml of benzyl chloroformate were added dropwise within 30 minutes under argon, with the pH of the solution being held between 9.5 and 11.5 by the dropwise addition of 10% sodium hydroxide solution. After completion of the addition the suspension was stirred at room temperature for 16 hours. The suspension was extracted with ethyl acetate, the organic phase was washed with water, dried over Na2SO4, filtered and the filtrate was concentrated. Purification of the crude product over a silica gel column gave 7.33 g of benzyl (R)-3-hydroxy-pyrrolidine-1-carboxylate as a beige liquid.

Workup

  1. temperaturecooled to 0°-5° C
  2. additionAfter completion of the addition the suspension
  3. extractionThe suspension was extracted with ethyl acetate
  4. washthe organic phase was washed with water
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated
  8. customPurification of the crude product over a silica gel column

Sources & evidence

ORD record
ord-d4435b786199453a92162ca8e91c4164
Source dataset
uspto-grants-1999_11
Patent number
US05977381

Reaction notes

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