Potassium Carbonate → (1R,2S)-[2-({[3-(4-fluoro-phenyl)-propyl]-methyl-amino}-methyl)-cyclohexyl]-carbamic Acid Benzyl Ester

HRID 1592326Notes

Reaction equation

HRID 1592326 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]1[CH2:17][CH2:16][CH2:15][CH2:14][C@H:13]1[CH2:18]OS(C1C=CC(C)=CC=1)(=O)=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:30][C:31]1[CH:36]=[CH:35][C:34]([CH2:37][CH2:38][CH2:39][NH:40][CH3:41])=[CH:33][CH:32]=1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH2:1]([O:8][C:9](=[O:10])[NH:11][C@@H:12]1[CH2:17][CH2:16][CH2:15][CH2:14][C@H:13]1[CH2:18][N:40]([CH2:39][CH2:38][CH2:37][C:34]1[CH:33]=[CH:32][C:31]([F:30])=[CH:36][CH:35]=1)[CH3:41])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 110842664-Fluoro-N-methyl-benzenepropanamineHCID 86599633toluene-4-sulfonic acid (1R,2R)-2-benzyloxycarbonylamino-cyclohexylmethyl Ester

Product 1

HCID 69424744(1R,2S)-[2-({[3-(4-fluoro-phenyl)-propyl]-methyl-amino}-methyl)-cyclohexyl]-carbamic Acid Benzyl EsterYield 64.2%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A solution of toluene-4-sulfonic acid (1R,2R)-2-benzyloxycarbonylamino-cyclohexylmethyl ester (632 mg, 1.51 mmol) in acetone (8 mL) was treated with N-[3-(4-fluorophenyl)-propyl]-methylamine (253 mg, 1.51 mmol) and potassium carbonate (209 mg, 1.51 mmol) and heated at reflux for 23.5 hours. The mixture was cooled and filtered, the solid was rinsed with acetone, and the filtrate was concentrated to provide a yellow-orange oil. Flash chromatography on silica gel, eluting with 50% ethyl acetate in hexane, followed by 50% ethyl acetate in hexane containing 5% ethanol, provided a light yellow viscous oil (400 mg, 64%).

Workup

  1. temperatureheated
  2. temperatureat reflux for 23.5 hours
  3. temperatureThe mixture was cooled
  4. filtrationfiltered
  5. washthe solid was rinsed with acetone
  6. concentrationthe filtrate was concentrated
  7. customto provide a yellow-orange oil
  8. washFlash chromatography on silica gel, eluting with 50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-779c18c5f592407a92d88f979c604e3e
Source dataset
uspto-grants-2007_11
Patent number
US07291744B2

Reaction notes

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