Benzyl Alcohol → HCID 45357422, compound

HRID 1009824Notes

Reaction equation

HRID 1009824 reaction equation
[CH2:1]([O:8][C@@H:9]1[CH2:13][CH2:12][NH:11][CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O[C@@H]1CCNC1.C(O)C1C=CC=CC=1.O.[C:29]1([CH3:39])[CH:34]=[CH:33][C:32]([S:35]([OH:38])(=[O:37])=[O:36])=[CH:31][CH:30]=1>C(O)(C)C.C(OCC)(=O)C>[C:29]1([CH3:39])[CH:30]=[CH:31][C:32]([S:35]([OH:38])(=[O:36])=[O:37])=[CH:33][CH:34]=1.[CH2:1]([O:8][C@@H:9]1[CH2:13][CH2:12][NH:11][CH2:10]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 244Benzyl AlcoholHCID 521998p-Toluenesulfonic acid monohydrateHCID 2759337(R)-3-PyrrolidinolHCID 16047991HCID 16047991, compound

Product 1

HCID 45357422HCID 45357422, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

1.0 g of a concentrate containing (R)-3-benzyloxypyrrolidine obtained in Example 15 (purity of 86.6%) containing (R)-3-hydroxypyrrolidine (content of 0.12 wt %) and benzyl alcohol (content of 1.9 wt %) as impurities were dissolved in 9 ml of isopropanol, followed by adding 0.93 g of p-toluenesulfonic acid monohydrate under ice cold conditions. After stirring for a while, the mixture was concentrated and dried under reduced pressure, thereby obtaining a white crystal. After the crude product was dispersed in 4.00 g of ethyl acetate and was heated to 40° C., 621 mg of isopropanol was added and the crude product was dissolved completely. The solution was gradually cooled to 22° C., and the deposited crystal was filtered under reduced pressure. The resultant wet crystal was washed with 10 ml of ethyl acetate, and then the wet crystal was dried under reduced pressure, thereby obtaining 1.15 g of dry crystal of (R)-3-benzyloxypyrrolidine p-toluenesulfonic acid (yield of 68%, purity of 100.0%). Each of (R)-3-hydroxypyrrolidine and benzyl alcohol in the crystal was 0.01 wt % or less.

Workup

  1. concentrationthe mixture was concentrated
  2. customdried under reduced pressure
  3. customobtaining a white crystal
  4. temperatureThe solution was gradually cooled to 22° C.
  5. filtrationthe deposited crystal was filtered under reduced pressure
  6. washThe resultant wet crystal was washed with 10 ml of ethyl acetate
  7. customthe wet crystal was dried under reduced pressure

Sources & evidence

ORD record
ord-e08314b018ba4c09ab9b0ef28697c070
Source dataset
uspto-grants-2011_07
Patent number
US07973176B2

Reaction notes

Loading…