Methanol → HCID 15430828, compound

HRID 430820Notes

Reaction equation

HRID 430820 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].CO.[BH4-].[Na+].P([O-])(O)(O)=O.[K+]>N1C=CC=CC=1>[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

6

Reactant 4

HCID 887MethanolHCID 516951Monobasic potassium phosphateHCID 4311764Sodium borohydrideHCID 15430829HCID 15430829, compound

Product 1

HCID 15430828HCID 15430828, compoundYield 100.8%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
80 °C

Procedure

An oven-dried 10 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 (0.216 g, 1 mmol) was charged to the flask followed by methanol (0.5 ml) and pyridine (1.5 ml) to give a solution. Sodium borohydride (0.046 g, 1.2 mmol) was added in a single portion and the mixture was heated to 80° C. The reaction was held at this temperature overnight, refluxed for 3 hours and then cooled to ambient. Saturated aqueous potassium dihydrogen phosphate (10 ml) was added to the reaction mass and the aqueous solution (pH7) was then extracted with ethyl acetate (3×10 ml). The combined organic layers were washed with brine (10 ml), dried (Na2SO4) and concentrated in vacuo to give 3-cyano-8-(2,2,2-trifluoroethyl)-8-azabicyclo[3.2.1]octane (0.22 g, 74% yield) as a mixture of epimers (12:1 equatorial:axial).

Workup

  1. customAn oven-dried 10 ml round bottom flask was fitted with a reflux condenser and magnetic stirrer
  2. additionthe apparatus filled with a nitrogen atmosphere
  3. customto give a solution
  4. customwas held at this temperature overnight
  5. temperaturerefluxed for 3 hours
  6. temperaturecooled
  7. extractionthe aqueous solution (pH7) was then extracted with ethyl acetate (3×10 ml)
  8. washThe combined organic layers were washed with brine (10 ml)
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1d868cf10ecc4a38bdef3ef6745e0048
Source dataset
uspto-grants-2001_11
Patent number
US06323343B1

Reaction notes

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