Dimethylacetamide → HCID 67125926, compound

HRID 929964Notes

Reaction equation

HRID 929964 reaction equation
Br[CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1.CC(N(C)C)=O.Br[C:23]1[CH:24]=[CH:25][C:26]([C:29]([O:31][CH3:32])=[O:30])=[N:27][CH:28]=1>C1COCC1.[Zn]>[C:12]([O:11][C:9]([N:6]1[CH2:7][CH2:8][CH:3]([CH2:2][C:23]2[CH:24]=[CH:25][C:26]([C:29]([O:31][CH3:32])=[O:30])=[N:27][CH:28]=2)[CH2:4][CH2:5]1)=[O:10])([CH3:15])([CH3:14])[CH3:13]

Participants

6

Reactant 3

HCID 31374DimethylacetamideHCID 7016458Methyl 5-bromopyridine-2-carboxylateHCID 15512811tert-Butyl 4-(bromomethyl)piperidine-1-carboxylate

Product 1

HCID 67125926HCID 67125926, compoundYield 17%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

Rieke Zinc (slightly excess by estimation) was stirred in 10 mL of THF under argon. tert-Butyl 4-(bromomethyl)piperidine-1-carboxylate (1.0 g, 3.6 mmol) in 5 mL of THF was added. The resulting mixture was stirred at rt for 3 h. The solution was then allowed to settle and the supernatant was transferred via a syringe to a stirred 5 mL of DMA solution. Methyl 5-bromopicolinate (0.78 g, 3.6 mmol) and Cl2Ni(Ph2PCH2CH2PPh2) were added sequentially, and the resulting mixture was stirred at rt for 60 h. LC-MS indicated a partial conversion. The reaction mixture was quenched with 15 mL of sat. NH4Cl, and extracted with 50 mL of EtOAc. The organic layer was washed with brine (20 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to give an oil which was purified by silica gel flash chromatography, eluting with 10-80% EtOAc in hexanes, to give methyl 5-((1-(tert-butoxycarbonyl)piperidin-4-yl)methyl)picolinate as a white solid (200 mg, 17%).

Workup

  1. stirringthe resulting mixture was stirred at rt for 60 h
  2. customThe reaction mixture was quenched with 15 mL of sat. NH4Cl
  3. extractionextracted with 50 mL of EtOAc
  4. washThe organic layer was washed with brine (20 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto give an oil which
  9. customwas purified by silica gel flash chromatography
  10. washeluting with 10-80% EtOAc in hexanes

Sources & evidence

ORD record
ord-b48155e5996c4654ba6bfd32c8707cf6
Source dataset
uspto-grants-2016_03
Patent number
US09296722B2

Reaction notes

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