Water → methyl 6-[(R)-3-[(R)-1-(naphthalen-1-yl)ethylamino]pyrrolidin-1-yl]-4-trifluoromethylnicotinate

HRID 452362

Reaction equation

HRID 452362 reaction equation
Cl.Cl.[C:3]1([C@H:13]([NH:15][C@@H:16]2[CH2:20][CH2:19][NH:18][CH2:17]2)[CH3:14])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=1.Cl[C:22]1[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:24][N:23]=1.C(=O)([O-])[O-].[K+].[K+].O>O1CCOCC1.C(OCC)(=O)C>[C:3]1([C@H:13]([NH:15][C@@H:16]2[CH2:20][CH2:19][N:18]([C:22]3[CH:31]=[C:30]([C:32]([F:33])([F:35])[F:34])[C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:24][N:23]=3)[CH2:17]2)[CH3:14])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 2775340Methyl 6-chloro-4-(trifluoromethyl)nicotinateHCID 67407230(R)-3-[(R)-1-(naphthalen-1-yl)ethylamino]pyrrolidine dihydrochloride

Product 1

HCID 58973503methyl 6-[(R)-3-[(R)-1-(naphthalen-1-yl)ethylamino]pyrrolidin-1-yl]-4-trifluoromethylnicotinate

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 157 mg of (R)-3-[(R)-1-(naphthalen-1-yl)ethylamino]pyrrolidine dihydrochloride and 120 mg of methyl 6-chloro-4-(trifluoromethyl)-nicotinate in 5 ml of dioxane was added 346 mg of potassium carbonate, and the reaction solution was stirred at 100° C. for 1 day. Further, to the reaction mixture was irradiated at 140° C. for 1 hour by using a Microwave reaction system, and then, the reaction mixture was cooled to room temperature. To the mixture were added water and ethyl acetate, and the mixture was stirred and the liquids were separated. The organic layer was dried and concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=80:20→50:50), and then, purified by NH thin layer silica gel column chromatography (hexane:ethyl acetate=67:33) to obtain methyl 6-[(R)-3-[(R)-1-(naphthalen-1-yl)ethylamino]pyrrolidin-1-yl]-4-trifluoromethylnicotinate (the following Table, Example, 12.001).

Workup

  1. customFurther, to the reaction mixture was irradiated at 140° C. for 1 hour
  2. customa Microwave reaction system
  3. temperaturethe reaction mixture was cooled to room temperature
  4. stirringthe mixture was stirred
  5. customthe liquids were separated
  6. customThe organic layer was dried
  7. concentrationconcentrated under reduced pressure
  8. customthe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=80:20→50:50)
  9. custompurified by NH thin layer silica gel column chromatography (hexane:ethyl acetate=67:33)

Sources & evidence

ORD record
ord-019d4dfc28a24958a4b13fbb79b494a9
Source dataset
uspto-grants-2013_07
Patent number
US08492111B2

Linked notes

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