Sodium Carbonate → HCID 15430829, compound

HRID 430826Notes

Reaction equation

HRID 430826 reaction equation
P(Cl)(Cl)(Cl)=O.CC(C)=O.C(=O)=O.[C:13]([C:15]1(O)[CH2:21][CH:20]2[N:22]([CH2:23][C:24]([F:27])([F:26])[F:25])[CH:17]([CH2:18][CH2:19]2)[CH2:16]1)#[N:14].C(=O)([O-])[O-].[Na+].[Na+]>N1C=CC=CC=1>[C:13]([C:15]1[CH2:16][CH:17]2[N:22]([CH2:23][C:24]([F:27])([F:26])[F:25])[CH:20]([CH2:19][CH2:18]2)[CH:21]=1)#[N:14]

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 24813Phosphorus oxychlorideHCID 18316935HCID 18316935, compoundHCID 18522661Acetone cardice

Product 1

HCID 15430829HCID 15430829, compoundYield 57.5%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
20 °C

Procedure

An oven-dried 25 ml 3-necked round bottom flask was fitted with a reflux condenser, thermometer and magnetic stirrer and the apparatus filled with nitrogen. Phosphorous oxychloride (1.41 g, 9.1 mmol) and pyridine (6.53 g) were charged to the flask and the mixture then cooled to −10° C. in an acetone/Drikold™ bath. 3-Cyano-3-hydroxy-8-(2,2,2-trifluoroethyl)-8-azabicyclo[3.2.1]octane (0.97 g, 4.1 mmol—assumed, prepared in Step 1) was added in one portion and the resultant exotherm raised the reaction mass temperature to 20° C. The mixture was then heated to 80° C. and held at this temperature for 24 hours, after which the reaction mixture was cooled and stirred at ambient for 18 hours. The reaction mass was poured onto ice/water (50 ml) and solid sodium carbonate was added portionwise until the mixture was adjusted to pH8. The mixture was extracted with ethyl acetate (3×30 ml), the combined extracts were dried (Na2SO4), filtered and concentrated in vacuo to give 3-cyano-8-(2,2,2-trifluoroethyl)-8-azabicyclo[3.2.1]oct-2-ene (0.51 g, 51% yield from 8-(2,2,2-trifluoroethyl)-8-azabicyclo[3.2.1]octan-3-one; 60:40 exo:endo cyano).

Workup

  1. customAn oven-dried 25 ml 3-necked round bottom flask was fitted with a reflux condenser
  2. additionthermometer and magnetic stirrer and the apparatus filled with nitrogen
  3. temperatureThe mixture was then heated to 80° C.
  4. temperatureafter which the reaction mixture was cooled
  5. additionwas added portionwise until the mixture
  6. extractionThe mixture was extracted with ethyl acetate (3×30 ml)
  7. dry with materialthe combined extracts were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0a657f2cb2594fb8bf60c1da97e51b8e
Source dataset
uspto-grants-2001_11
Patent number
US06323343B1

Reaction notes

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