1,2-Diaminocyclohexane, trans- → (5S)-1-{4-[3-(2-methylpyrrolidin-1-yl)propoxyl]phenyl}-5-(piperidin-1-ylmethyl)pyrrolidin-2-one

HRID 548634Notes

Reaction equation

HRID 548634 reaction equation
I[C:2]1[CH:17]=[CH:16][C:5]([O:6][CH2:7][CH2:8][CH2:9][N:10]2[CH2:14][CH2:13][CH2:12][CH:11]2[CH3:15])=[CH:4][CH:3]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].N[C@@H]1CCCC[C@H]1N.[N:34]1([CH2:40][C@H:41]2[NH:45][C:44](=[O:46])[CH2:43][CH2:42]2)[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1>O1CCOCC1.ClCCl.[Cu](I)I>[CH3:15][CH:11]1[CH2:12][CH2:13][CH2:14][N:10]1[CH2:9][CH2:8][CH2:7][O:6][C:5]1[CH:16]=[CH:17][C:2]([N:45]2[C@H:41]([CH2:40][N:34]3[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39]3)[CH2:42][CH2:43][C:44]2=[O:46])=[CH:3][CH:4]=1

Participants

8

Reactant 4

HCID 438061,2-Diaminocyclohexane, trans-HCID 62657Potassium Phosphate, TribasicHCID 57550249(5S)-5-(piperidin-1-ylmethyl)pyrrolidin-2-oneHCID 575502501-[3-(4-Iodophenoxy)propyl]-2-methylpyrrolidine

Product 1

HCID 16662453(5S)-1-{4-[3-(2-methylpyrrolidin-1-yl)propoxyl]phenyl}-5-(piperidin-1-ylmethyl)pyrrolidin-2-oneYield 46%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A suspension of 1-[3-(4-iodophenoxy)propyl]-2-methylpyrrolidine a5 (0.245 g, 0.71 mmol, 1 eq) in dioxan (4 ml), potassium phosphate (0.3 g, 1.42 mmol, 2 eq), copper iodide (0.001 g, 0.007 mmol, 1 mol %), trans-1,2-diaminocyclohexane (0.008 g, 0.07 mmol, 10 mol %) and (5S)-5-(piperidin-1-ylmethyl)pyrrolidin-2-one a15 (0.155 g, 0.85 mmol, 1.2 eq) is placed in a sealed tube under argon atmosphere and heated at 110° C. until reaction completion. The mixture is diluted with dichloromethane and is washed twice with a solution of 1 M sodium hydroxide. The organic layer is dried over magnesium sulfate and concentrated in vacuo to give 279 mg of a brown oil. This oil is purified by chromatography on silicagel (dichloromethane/ethanol/ammonia 95/5/0.5) to afford 130 mg of (5S)-1-{4-[3-(2-methylpyrrolidin-1-yl)propoxyl]phenyl}-5-(piperidin-1-ylmethyl)pyrrolidin-2-one 48 as a pink oil.

Workup

  1. customis placed in a sealed tube under argon atmosphere
  2. washis washed twice with a solution of 1 M sodium hydroxide
  3. dry with materialThe organic layer is dried over magnesium sulfate
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-59dad73e12e6424cb6d251c2464fa6b7
Source dataset
uspto-grants-2011_05
Patent number
US07943605B2

Reaction notes

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