p-Toluenesulfonic acid monohydrate → [(R)-1-(5-Bromo-3-methyl-pyridin-2-yl)-pyrrolidin-3-yl]-dimethyl-amine

HRID 423396

Reaction equation

HRID 423396 reaction equation
Br[C:2]1[C:7]([CH3:8])=[CH:6][C:5]([Br:9])=[CH:4][N:3]=1.[CH3:10][N:11]([CH3:17])[C@@H:12]1[CH2:16][CH2:15][NH:14][CH2:13]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CCOC(C)=O>[Br:9][C:5]1[CH:6]=[C:7]([CH3:8])[C:2]([N:14]2[CH2:15][CH2:16][C@@H:12]([N:11]([CH3:17])[CH3:10])[CH2:13]2)=[N:3][CH:4]=1

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 8176802,5-Dibromo-3-methylpyridineHCID 2758521(3R)-(+)-3-(Dimethylamino)pyrrolidine

Product 1

HCID 66673852[(R)-1-(5-Bromo-3-methyl-pyridin-2-yl)-pyrrolidin-3-yl]-dimethyl-amineYield 99%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Combine 2,5-dibromo-3-methyl-pyridine (2.00 g, 7.97 mmol) with dimethyl-(R)-pyrrolidin-3-yl-amine (2.40 g, 20.72 mmol) and p-toluenesulfonic acid monohydrate (0.39 g, 2.07 mmol) in a sealed tube and heat at 100° C. overnight. Dilute with EtOAc (100 mL), wash with saturated NaHCO3 (3×40 mL), dry over Na2SO4, filter and concentrate. Purify the crude material by chromatography, eluting with 2% NH3H2O in 1:1 CH3OH:EtOAc to give 2.09 g (99%) of the title compound. LC-MS/ES m/z (79Br) 284.3 [M+H]+.

Workup

  1. washwash with saturated NaHCO3 (3×40 mL)
  2. dry with materialdry over Na2SO4
  3. filtrationfilter
  4. concentrationconcentrate
  5. customPurify the crude material by chromatography
  6. washeluting with 2% NH3H2O in 1:1 CH3OH

Sources & evidence

ORD record
ord-47b41fdcf37f467cb71fdf6c783827d3
Source dataset
uspto-grants-2012_01
Patent number
US08101764B2

Linked notes

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