HCID 62958818, compound → HCID 70896544, compound

HRID 1619285Notes

Reaction equation

HRID 1619285 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([N:10]2[CH2:15][CH2:14][C:13](=[O:16])[CH2:12][CH2:11]2)=[O:9])=[N:6][CH:7]=1.[CH3:17][Mg]Br>C1COCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([N:10]2[CH2:11][CH2:12][C:13]([OH:16])([CH3:17])[CH2:14][CH2:15]2)=[O:9])=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 62958818HCID 62958818, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 70896544HCID 70896544, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
2.5 °C

Procedure

1-(5-Bromo-pyridine-2-carbonyl)-piperidin-4-one (Example 37, step 1) (135 mg, 0.48 mmol) was dissolved in THF (3 ml) and the mixture was cooled to 0-5° C. 3M Methylmagnesium bromide (190 μl, 0.57 mmol, 1.2 equiv.) was added drop wise at 0-5° C. and the mixture was stirred for 2 hours at 0-5° C. The reaction mixture was extracted with saturated NH4Cl solution and two times with ethyl acetate. The organic layers were extracted with water and brine, dried over sodium sulfate and evaporated to dryness. The crude product was purified by flash chromatography with a 20 g silica gel column and eluting with heptane:ethyl acetate 100:0→0:100. The desired (5-bromo-pyridin-2-yl)-(4-hydroxy-4-methyl-piperidin-1-yl)-methanone (35 mg, 25% yield) was obtained as a colorless oil, MS: m/e=299.2/301.1 (M+H+).

Workup

  1. extractionThe reaction mixture was extracted with saturated NH4Cl solution and two times with ethyl acetate
  2. extractionThe organic layers were extracted with water and brine
  3. dry with materialdried over sodium sulfate
  4. customevaporated to dryness
  5. customThe crude product was purified by flash chromatography with a 20 g silica gel column
  6. washeluting with heptane:ethyl acetate 100:0→0:100

Sources & evidence

ORD record
ord-2a487eb4d1f74518be06d3111f9ba7a2
Source dataset
uspto-grants-2014_07
Patent number
US08772300B2

Reaction notes

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