Pyrrolidine → (S)-1,4-di(t-butoxycarbonyl)-2-(4-((S)-3-(pyrrolidin-1-yl) pyrrolidin-1-yl)phenyl)piperazine

HRID 1784681Notes

Reaction equation

HRID 1784681 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][C@@H:9]1[C:21]1[CH:26]=[CH:25][C:24](N2CC[C@@H](OS(C)(=O)=O)C2)=[CH:23][CH:22]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:37]1[CH2:41][CH2:40][CH2:39][CH2:38]1>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][C@@H:9]1[C:21]1[CH:22]=[CH:23][C:24]([N:37]2[CH2:41][CH2:40][C@H:39]([N:37]3[CH2:41][CH2:40][CH2:39][CH2:38]3)[CH2:38]2)=[CH:25][CH:26]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 31268PyrrolidineHCID 53628945(S)-1,4-di(t-butoxycarbonyl)-2-(4-((R)-3-methansulfonyloxy-pyrrolidino)phenyl)piperazine

Product 1

HCID 67117414(S)-1,4-di(t-butoxycarbonyl)-2-(4-((S)-3-(pyrrolidin-1-yl) pyrrolidin-1-yl)phenyl)piperazineYield 58.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of (S)-1,4-di(t-butoxycarbonyl)-2-(4-((R)-3-methansulfonyloxy-pyrrolidino)phenyl)piperazine (877 mg, 1.64 mmol) in toluene (10 mL) was added pyrrolidine (0.64 mL, 8.19 mmol), and the resulting solution was heated at 90° C. for 8 h. After checking consumption of the starting material with TLC, the reaction mixture was partitioned between ethyl acetate and saturated sodium bicarbonate aqueous solution. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting 30-100% ethyl acetate-hexane and then 3-10% methanol-ethyl acetate to afford (S)-1,4-di(t-butoxycarbonyl)-2-(4-((S)-3-(pyrrolidin-1-yl)pyrrolidin-1-yl)phenyl)piperazine (479 mg, 58%) as a pale yellow powder.

Workup

  1. customconsumption of the starting material with TLC
  2. customthe reaction mixture was partitioned between ethyl acetate and saturated sodium bicarbonate aqueous solution
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel column chromatography
  7. washeluting 30-100% ethyl acetate-hexane

Sources & evidence

ORD record
ord-6f79941e7f1e45968fcc77f4f8f261b8
Source dataset
uspto-grants-2009_03
Patent number
US07504411B2

Reaction notes

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