Methyl acetoacetate → HCID 22477278, compound

HRID 549032Notes

Reaction equation

HRID 549032 reaction equation
[C:1](OC)(=O)[CH2:2][C:3]([CH3:5])=[O:4].[H-].[Na+].CCCCCCC.C(C([C:27]1[C:35]2[C:30](=[N:31][CH:32]=[CH:33][N:34]=2)[NH:29][C:28]=1[C:36]1[CH:41]=[CH:40][C:39]([C:42]([CH3:45])([CH3:44])[CH3:43])=[CH:38][CH:37]=1)(C)C(OC)=O)(=O)C>CN1CCCC1=O.[OH-].[Na+].CO.O1CCCC1.C(OCC)(=O)C>[C:42]([C:39]1[CH:40]=[CH:41][C:36]([C:28]2[NH:29][C:30]3=[N:31][CH:32]=[CH:33][N:34]=[C:35]3[C:27]=2[CH2:1][CH2:2][C:3](=[O:4])[CH3:5])=[CH:37][CH:38]=1)([CH3:44])([CH3:43])[CH3:45]

Participants

10

Reactant 4

HCID 7757Methyl acetoacetateHCID 8900HeptaneHCID 24758Sodium hydrideHCID 131728845HCID 131728845, compound

Product 1

HCID 22477278HCID 22477278, compound

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×HCID 14798Sodium HydroxideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of methyl acetoacetate (1.35 mL) in N-methylpyrrolidone (15 mL), cooled to 0° C., was treated portionwise with sodium hydride (0.33 g, 60% dispersion in mineral oil) and after stirring at 0° C. for 30 minutes this mixture was then treated with a solution of [6-(4-tert-butylphenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]methyltrimethylammonium iodide [2 g, Reference Example 45(a)] in N-methylpyrrolidone (100 mL). After stirring at room temperature overnight the reaction mixture was subjected to chromatography on silica eluting with a mixture of heptane and ethyl acetate. The resulting 2-acetyl-[6-(4-tert-butyl-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propionic acid, methyl ester (1.2 g) was dissolved in a mixture of sodium hydroxide (250 mL, 2N), methanol (25 mL) and tetrahydrofuran. This solution was then heated at 50° C. for 1 hour, then evaporated, then acidified by addition of hydrochloric acid (25 mL, 2N) and then extracted with ethyl acetate. The organic extract was dried over sodium sulfate and then evaporated to give the title compound (1 g). MS: 322 (MH+).

Workup

  1. stirringAfter stirring at room temperature overnight the reaction mixture
  2. temperatureThis solution was then heated at 50° C. for 1 hour
  3. customevaporated
  4. additionacidified by addition of hydrochloric acid (25 mL, 2N)
  5. extractionextracted with ethyl acetate
  6. extractionThe organic extract
  7. dry with materialwas dried over sodium sulfate
  8. customevaporated

Sources & evidence

ORD record
ord-a7d1a60fb9b14be79a2ac575125fcf2c
Source dataset
uspto-grants-2011_05
Patent number
US07943616B2

Reaction notes

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