Trifluoromethanesulfonic acid → HCID 58973476, compound

HRID 409597Notes

Reaction equation

HRID 409597 reaction equation
O[C@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.C(N(C(C)C)CC)(C)C.FC(F)(F)S(O)(=O)=O.[CH3:31][O:32][C:33]1[CH:34]=[C:35]([C@H:39]([NH2:41])[CH3:40])[CH:36]=[CH:37][CH:38]=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(Cl)(Cl)Cl>[CH3:31][O:32][C:33]1[CH:34]=[C:35]([C@H:39]([NH:41][CH:2]2[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]2)[CH3:40])[CH:36]=[CH:37][CH:38]=1

Participants

8

Reactant 5

HCID 62406Trifluoromethanesulfonic acidHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 854055tert-Butyl (3S)-3-hydroxypyrrolidine-1-carboxylateHCID 7020759(R)-1-(3-Methoxyphenyl)ethylamine

Product 1

HCID 58973476HCID 58973476, compoundYield 45.2%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-20 °C

Procedure

To a solution of 25 g of tert-butyl (S)-3-hydroxypyrrolidine-1-carboxylate and 25.9 g of diisopropylethylamine dissolved in 500 ml of methylene chloride was added dropwise 100 ml of a solution of 49 g of anhydrous trifluoromethanesulfonic acid in methylene chloride at −20° C. or lower. The reaction mixture was stirred for 15 minutes while maintaining it to −20° C., and then, to the mixture was added dropwise 100 ml of a solution of 24.2 g of (R)-1-(3-methoxyphenyl)ethylamine in methylene chloride at −20° C. or lower, and the reaction mixture was stirred at room temperature for 16 hours. To the reaction mixture were added a saturated aqueous sodium bicarbonate solution and chloroform, the mixture was stirred and the liquids were separated. The organic layer was dried and the solvent was evaporated, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1→1:2) to obtain 19.32 g of tert-butyl 3-[(R)-1-(3-methoxyphenyl)ethylamino]pyrrolidine-1-carboxylate. (2) To a solution of 19.32 g of tert-butyl 3-[(R)-1-(3-methoxyphenyl)ethylamino]pyrrolidine-1-carboxylate dissolved in 30 ml of chloroform was added 300 ml of a solution of 4M hydrochloric acid in dioxane, and the mixture was stirred at room temperature for 16 hours. The resulting precipitates were collected by filtration, washed with ethyl acetate, and recrystallized from methanol and tetrahydrofuran twice to obtain 8.54 g of (R)-3-[(R)-1-(3-methoxyphenyl)ethylamino]pyrrolidine dihydrochloride (the following Reference example Table, Reference example 1.003).

Workup

  1. stirringlower, and the reaction mixture was stirred at room temperature for 16 hours
  2. stirringthe mixture was stirred
  3. customthe liquids were separated
  4. customThe organic layer was dried
  5. customthe solvent was evaporated
  6. customthe residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1→1:2)

Sources & evidence

ORD record
ord-7cfb94d2a8db453ca00892e720f39199
Source dataset
uspto-grants-2014_06
Patent number
US08759387B2

Reaction notes

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