Sodium Carbonate → HCID 15430829, compound

HRID 430830Notes

Reaction equation

HRID 430830 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 94.9%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
12 °C

Procedure

A dry 25 ml 3-necked round bottom flask was fitted with a reflux condenser, thermometer and magnetic stirrer and the apparatus was filled with a nitrogen atmosphere. Phosphorous oxychloride (1.34, 8.7 mmol) and pyridine (6.22 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-azabicycio[3.2.1]octane (0.92 g, 3.9 mmol—assumed, prepared in Step 1) was added in one portion and the resultant exotherm raised the reaction mass temperature to 12° C. The mixture was heated to 80° C. and held at this temperature for 23 hours after which the mixture was cooled to ambient. The reaction mixture was poured onto ice/water (50 ml) and sodium carbonate added portionwise until the mixture was adjusted to pH8. The resulting 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 (0.8 g, 72% yield from 8-(2,2,2-trifluoroethyl)-8-azabicyclo[3.2.1]-octan-3-one; 74:26 exo:endo cyano).

Workup

  1. customA dry 25 ml 3-necked round bottom flask was fitted with a reflux condenser
  2. additionthermometer and magnetic stirrer and the apparatus was filled with a nitrogen atmosphere
  3. temperatureThe mixture was heated to 80° C.
  4. temperatureafter which the mixture was cooled
  5. additionadded portionwise until the mixture
  6. extractionThe resulting 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-c4a51f7007274b66af8c16c2906427c3
Source dataset
uspto-grants-2001_11
Patent number
US06323343B1

Reaction notes

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