Hydrochloric Acid → (3R)-1-[(1R,2R)-2-[2-(3-benzyloxy-4-methoxy-phenyl)ethoxy]cyclohexyl]-3-pyrrolidinol

HRID 2355795Notes

Reaction equation

HRID 2355795 reaction equation
C([O:4][C@@H:5]1[CH2:9][C:8](=O)[N:7]([C@@H:11]2[CH2:16][CH2:15][CH2:14][CH2:13][C@H:12]2[O:17][CH2:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH:21]=2)[C:6]1=O)(=O)C.Cl>C1COCC1>[CH2:29]([O:28][C:22]1[CH:21]=[C:20]([CH2:19][CH2:18][O:17][C@@H:12]2[CH2:13][CH2:14][CH2:15][CH2:16][C@H:11]2[N:7]2[CH2:8][CH2:9][C@@H:5]([OH:4])[CH2:6]2)[CH:25]=[CH:24][C:23]=1[O:26][CH3:27])[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 58856245(1R,2R)-1-{2-[2-(3-Benzyloxy-4-methoxy-phenyl)ethoxy]cyclohexyl}-2,5-dioxopyrrolidin-3-(R)-yl acetate

Product 1

HCID 66686409(3R)-1-[(1R,2R)-2-[2-(3-benzyloxy-4-methoxy-phenyl)ethoxy]cyclohexyl]-3-pyrrolidinolYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (1R, 2R)-1-{2-[2-(3-Benzyloxy-4-methoxy-phenyl)ethoxy]cyclohexyl}-2,5-dioxopyrrolidin-3-(R)-yl acetate (42.0 g, 84.8 mmol) in anhydrous THF (300 mL) at 0° C. was added borane-THF complex solution (1.0 M, 297 mL, 3.5 mol equivalents) under N2 via an addition funnel over a period of 60 minutes. The reaction mixture was heated to reflux for 60 minutes. The reaction mixture was cooled to 0° C. and quenched slowly by addition of methanol (˜15 mL). The reaction mixture was concentrated under reduced pressure to remove the THF and to the residue was added methanolic-HCl solution (˜1.25 M in methanol, 297 mL, 3.5 equivalents). The solution was then heated at 70-80° C. for 2 hours. The reaction mixture was cooled to ambient temperature and concentrated under reduced pressure to give (3R)-1-[(1R,2R)-2-[2-(3-benzyloxy-4-methoxy-phenyl)ethoxy]cyclohexyl]-3-pyrrolidinol as a colorless syrup (35.0 g, 89% yield). The sample was used directly without further purification in the next step.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 60 minutes
  3. customquenched slowly by addition of methanol (˜15 mL)
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. customto remove the THF
  6. temperatureThe solution was then heated at 70-80° C. for 2 hours
  7. temperatureThe reaction mixture was cooled to ambient temperature
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-17d9e1ab62f6435b925e488777bd3009
Source dataset
uspto-grants-2010_07
Patent number
US07754897B2

Reaction notes

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