Acetic Acid → (+/-)-(5-Bromo-pyridin-2-yl)-(1-methyl-pyrrolidin-3-yl)-methanone

HRID 423395Notes

Reaction equation

HRID 423395 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([CH:10]2[CH2:14][CH2:13][NH:12][CH2:11]2)=[O:9])=[N:6][CH:7]=1.[C:15](O)(=O)C.C=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([CH:10]2[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11]2)=[O:9])=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 66673744(5-Bromo-pyridin-2-yl)-pyrrolidin-3-yl-methanone

Product 1

HCID 66673965(+/-)-(5-Bromo-pyridin-2-yl)-(1-methyl-pyrrolidin-3-yl)-methanoneYield 47%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (5-bromo-pyridin-2-yl)-pyrrolidin-3-yl-methanone (0.35 g, 1.35 mmol) in methanol (68 mL), add acetic acid (0.15 mL, 2.7 mmol), and formaldehyde (0.33 g, 4.1 mmol, 37% aqueous solution). After 15 min, add sodium triacetoxyborohydride (0.86 g, 4.1 mmol) and allow the mixture to stir at RT for 1 h. Concentrate the reaction mixture, dissolve in CH2Cl2, and wash with saturated NaHCO3. Back-extract the aqueous with CH2Cl2. Wash the combined organic layer with water, dry over Na2SO4, filter, and concentrate. Purify the crude material by flash chromatography, eluting with 5-10% MeOH (2N NH3)/CH2Cl2 to give 0.17 g (47%) of the title compound. LC-MS/ES m/z (79Br) 270 [M+H]+.

Workup

  1. concentrationConcentrate the reaction mixture
  2. dissolutiondissolve in CH2Cl2
  3. washwash with saturated NaHCO3
  4. extractionBack-extract the aqueous with CH2Cl2
  5. washWash the combined organic layer with water
  6. dry with materialdry over Na2SO4
  7. filtrationfilter
  8. concentrationconcentrate
  9. customPurify the crude material by flash chromatography
  10. washeluting with 5-10% MeOH (2N NH3)/CH2Cl2

Sources & evidence

ORD record
ord-0900ae6c219e49d29143fe45dd2aef97
Source dataset
uspto-grants-2012_01
Patent number
US08101764B2

Reaction notes

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