Diisopropylamine → 3-Methyl-1-(2-(methylthio)pyrimidin-4-yl)butan-2-one

HRID 383725Notes

Reaction equation

C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][C:14]1[CH:19]=[CH:18][N:17]=[C:16]([S:20][CH3:21])[N:15]=1.[C:22](OC)(=[O:26])[CH:23]([CH3:25])[CH3:24]>C1COCC1.CCCCCC>[CH3:24][CH:23]([CH3:25])[C:22](=[O:26])[CH2:13][C:14]1[CH:19]=[CH:18][N:17]=[C:16]([S:20][CH3:21])[N:15]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of diisopropylamine (10.1 mL, 71.8 mmol) in anhydrous THF (50 mL) is added n-butyllithum (33.6 mL of an 1.6M in hexane) dropwise at 0° C. After 30 min at 0° C., 4-methyl-2-(methylthio)pyrimidine (5 mL, 35.9 mmol) is added. The resulting mixture is stirred at 0° C. for 30 min. After the addition of methyl isobutyrate (4.3 mL, 37.7 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 40:60) to give 4.3 g of 3-methyl-1-(2-methylsulfanyl-pyrimidin-4-yl)-butan-2-one.

Workup

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

Sources & evidence

ORD record: ord-b2f115a8ca7e4413aaa8aef849006015
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08367687B2

Reaction notes

Loading…