Methanol, magnesium salt (2:1) → HCID 15430828, compound

HRID 430821Notes

Reaction equation

HRID 430821 reaction equation
[C:1]([C:3]1[CH2:9][CH:8]2[N:10]([CH2:11][C:12]([F:15])([F:14])[F:13])[CH:5]([CH2:6][CH2:7]2)[CH:4]=1)#[N:2].[Mg].C[O-].[Mg+2].C[O-].P([O-])(O)(O)=O.[K+]>O.CO>[C:1]([CH:3]1[CH2:4][CH:5]2[N:10]([CH2:11][C:12]([F:15])([F:14])[F:13])[CH:8]([CH2:7][CH2:6]2)[CH2:9]1)#[N:2]

Participants

7

Reactant 4

HCID 164537Methanol, magnesium salt (2:1)HCID 516951Monobasic potassium phosphateHCID 5462224MagnesiumHCID 15430829HCID 15430829, compound

Product 1

HCID 15430828HCID 15430828, compoundYield 275%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

An oven-dried 50 ml round bottom flask was fitted with a reflux condenser and magnetic stirrer and the apparatus filled with a nitrogen atmosphere. 3-Cyano-8-(2,2,2-trifluoroethyl)-8-azabicyclo[3.2.1]oct-2-ene (0.26 g, 1 mmol) was charged to the reactor followed by methanol (10 ml). Magnesium turnings (1.0 g, 40 mmol) were added in a single portion and after an induction period of 0.25 hours, a vigorous reaction occurred which was moderated by cooling with an ice bath. The mixture was stirred at 0° C. for 1 hour, during which time the reaction mass thickened (due to magnesium methoxide formation), and was then allowed to warm to ambient. The reaction mixture was added to a solution of potassium dihydrogen phosphate (10 g) in water (40 ml) and stirred for 0.5 hour. Residual solid was removed by filtration and the aqueous filtrate was extracted with ethyl acetate (3×20 ml). The combined organic layers were washed with brine (20 ml), dried (Na2SO4) and concentrated in vacuo to give 3-cyano-8-(2,2,2-trifluoroethyl)-8-azabicyclo[3.2.1]octane (0.6 g, 72% yield) as a mixture of epimers (25:75 exo:endo).

Workup

  1. customAn oven-dried 50 ml round bottom flask was fitted with a reflux condenser and magnetic stirrer
  2. additionthe apparatus filled with a nitrogen atmosphere
  3. customafter an induction period of 0.25 hours, a vigorous reaction
  4. temperatureby cooling with an ice bath
  5. temperatureto warm to ambient
  6. stirringstirred for 0.5 hour
  7. customResidual solid was removed by filtration
  8. extractionthe aqueous filtrate was extracted with ethyl acetate (3×20 ml)
  9. washThe combined organic layers were washed with brine (20 ml)
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2ac71026f71845bd8f0025620b081880
Source dataset
uspto-grants-2001_11
Patent number
US06323343B1

Reaction notes

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