Diethyl Ether → HCID 91259109, compound

HRID 564391Notes

Reaction equation

HRID 564391 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][C:12](=O)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.[NH:16]1[CH2:20][CH2:19][C@@H:18]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:17]1.CCOCC>CO>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH:12]([N:16]3[CH2:20][CH2:19][C@@H:18]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:26])([CH3:25])[CH3:27])[CH2:17]3)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 1514397(3R)-(+)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 212605551-(4-Methoxyphenyl)piperidin-4-one

Product 1

HCID 91259109HCID 91259109, compoundYield 67.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 1-(4-methoxyphenyl)piperidin-4-one (5.65 g, 27.6 mmol) and (R)-tert-butyl pyrrolidin-3-ylcarbamate (5.65 g, 30.3 mmol) in MeOH (200 mL) was added STAB (10.49 g, 49.5 mmol) in small portions. The reaction mixture was stirred overnight, then was concentrated to 1/10 of the original volume. NaOH (100 mL, 1N aqueous) and CH2Cl2 (100 mL) were added and the organic layer was washed with brine, dried over Mg2SO4, filtered and concentrated. Upon the addition of ether, tert-butyl {(3R)-1-[1-(4-methoxyphenyl)piperidin-4-yl]pyrrolidin-3-yl}carbamate (6.98 g, yield 67.5%) precipitated as a white solid. The resulting solid was dissolved in CH2Cl2 (50 mL) to which was added 4N HCl/dioxane (50 mL). After 2 h at room temperature, ether was added until (3R)-1-[1-(4-methoxyphenyl)piperidin-4-yl]pyrrolidin-3-amine precipitated (as the HCl salt) from the solution, and was collected by filtration as a white solid (6.40 g, 52% over 2 steps).

Workup

  1. concentrationwas concentrated to 1/10 of the original volume
  2. additionNaOH (100 mL, 1N aqueous) and CH2Cl2 (100 mL) were added
  3. washthe organic layer was washed with brine
  4. dry with materialdried over Mg2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-81736cb4f5084769bb578155ce99202f
Source dataset
uspto-grants-2011_11
Patent number
US08067457B2

Reaction notes

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