Diisopropylamine → HCID 44597011, compound

HRID 383721Notes

Reaction equation

HRID 383721 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[F:13][C:14]1[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][N:15]=1.[C:21](OC)(=[O:25])[CH:22]([CH3:24])[CH3:23]>C1COCC1.CCCCCC>[F:13][C:14]1[CH:19]=[C:18]([CH2:20][C:21](=[O:25])[CH:22]([CH3:24])[CH3:23])[CH:17]=[CH:16][N:15]=1

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 11039Methyl isobutyrateHCID 27374032-Fluoro-4-methylpyridineHCID 178418339Butyllithium

Product 1

HCID 44597011HCID 44597011, compoundYield 58.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of diisopropylamine (12.6 mL, 89.9 mmol) in anhydrous THF (50 mL) is added n-butyllithum (42.2 mL of an 1.6M in hexane) dropwise at 0° C. After 30 min at 0° C., 2-fluoro-4-methylpyridine (5 g, 45 mmol) is added. The resulting mixture is stirred at 0° C. for 30 min. After the addition of methyl isobutyrate (5.4 mL, 47.3 mmol) at 0° C., the reaction mixture is stirred overnight. The reaction mixture is quenched with acetic acid at 0° C., diluted with water, and extracted with ethyl ether. The organic layer is dried over sodium sulfate and concentrated in vacuo. The residue is purified by flash chromatography (SiO2, EtOAc/heptane 7:93 to 60:40) to give 4.8 g of 1-(2-fluoro-pyridin-4-yl)-3-methyl-butan-2-one as a light yellowish solid.

Workup

  1. stirringthe reaction mixture is stirred overnight
  2. customThe reaction mixture is quenched with acetic acid at 0° C.
  3. additiondiluted with water
  4. extractionextracted with ethyl ether
  5. dry with materialThe organic layer is dried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified by flash chromatography (SiO2, EtOAc/heptane 7:93 to 60:40)

Sources & evidence

ORD record
ord-aa8ece56a44740a1b78a93d6815986af
Source dataset
uspto-grants-2013_02
Patent number
US08367687B2

Reaction notes

Loading…