Carbon Dioxide → 1-(2-Phenylpyrimidin-5-yl)ethanone

HRID 42287

Reaction equation

HRID 42287 reaction equation
CON(C)[C:4]([C:6]1[CH:7]=[N:8][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[N:10][CH:11]=1)=[O:5].[C:19](=O)=O.C[Mg]Cl.[Cl-].[NH4+]>C1COCC1.C(OCC)C.C(O)C>[C:12]1([C:9]2[N:10]=[CH:11][C:6]([C:4](=[O:5])[CH3:19])=[CH:7][N:8]=2)[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

8

Reactant 4

HCID 280Carbon DioxideHCID 25517Ammonium ChlorideHCID 47401292N-methoxy-N-methyl-2-phenylpyrimidine-5-carboxamideHCID 178418332HCID 178418332, compound

Product 1

HCID 226310721-(2-Phenylpyrimidin-5-yl)ethanoneYield 78%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-60 °C

Procedure

A solution consisting of N-methoxy-N-methyl-2-phenylpyrimidine-5-carboxamide (Step I, 1.80 g, 7.39 mmol) in anhydrous THF (20 mL) was cooled in a −60° C. bath (ethanol, CO2(s)). Methylmagnesium chloride (Aldrich, 3.0 M in THF, 2.75 mL, 8.14 mmol) was subsequently added dropwise to the reaction mixture. The reaction mixture was stirred for 30 minutes in the −60° C. bath and was subsequently allowed to warm to room temperature over one hour. The crude reaction mixture was then poured into a separatory funnel that contained diethyl ether (200 mL) and saturated ammonium chloride (150 mL). The organic layer was separated and the aqueous layer was washed again with diethyl ether (100 mL). The combined organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to afford a white solid as the crude product. The crude solid was triturated with a hexane-ethyl acetate (9:1 v/v) mixture (20 mL). The precipitate in solution was filtered to afford the title compound as a white solid (1.15 g, 78% yield); Rf 0.72 with 1:1 v/v hexanes-ethyl acetate; 1H-NMR (400 MHz; CDCl3) δ 9.25 (s, 2H), 8.53 (dd, 2H), 7.58 (m, 3H), 2.63 (s, 3H); MS (APCI+) m/z 199.0 (M+1).

Workup

  1. temperatureto warm to room temperature over one hour
  2. customThe crude reaction mixture
  3. additionwas then poured into a separatory funnel that
  4. customThe organic layer was separated
  5. washthe aqueous layer was washed again with diethyl ether (100 mL)
  6. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto afford a white solid as the crude product
  10. customThe crude solid was triturated with a hexane-ethyl acetate (9:1 v/v) mixture (20 mL)
  11. filtrationThe precipitate in solution was filtered

Sources & evidence

ORD record
ord-09b51270ec5243579846fbc0216bf398
Source dataset
uspto-grants-2013_09
Patent number
US08536185B2

Linked notes

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