Sodium hydride → 4-Chloro-6-((R)-1-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)ethoxy)-2-(4-fluorobenzylthio)pyrimidine

The sub-title product of step (ii) (85.7 g) and 60% sodium hydride (14.2 g) were suspended in tetrahydrofuran (1000 mL) and cooled in ice/water for 30 minutes. A solution of (R)-1-((S)-2,2-Dimethyl-1,3-dioxolan-4-yl)ethanol (Intermediate A) in 2-methyltetrahydrofuran (53% w/v) (104 mL) was added dropwise over 20 minutes and the reaction was stirred at 0° C. to room temperature for 20 hours. The reaction was partitioned between water (500 mL) and ethyl acetate (500 mL). The aqueous was re-extracted with ethyl acetate (2×500 mL) and the combined organics were dried and evaporated in vacuo. The crude material was purified by flash silica chromatography with gradient elution 0-30% ethyl acetate in isohexane using Isolera LS. Pure fractions were evaporated to dryness to afford to afford the sub-title product (94 g) as a yellow oil.

1. customThe reaction was partitioned between water (500 mL) and ethyl acetate (500 mL)
2. extractionThe aqueous was re-extracted with ethyl acetate (2×500 mL)
3. customthe combined organics were dried
4. customevaporated in vacuo
5. customThe crude material was purified by flash silica chromatography with gradient elution 0-30% ethyl acetate in isohexane using Isolera LS
6. customPure fractions were evaporated to dryness
7. customto afford

ORD 기록

ord-1f6d75be169b4ed98110e1680fe3154b

출처 데이터셋

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09221782B2