反応 #57290

反応方程式

6

[4-(2-methoxy-ethoxymethoxy)-2-(2,2,2-trifluoro-acetyl)-phenyl]-carbamic Acid Tert-Butyl Ester

ammonium chloride

n-butyl lithium

ethynyl-cyclopropane

→

7

収率 61.0%

[2-(3-cyclopropyl-1-hydroxy-1-trifluoromethyl-prop-2-ynyl)-4-(2-methoxy-ethoxymethoxy)-phenyl]-carbamic Acid Tert-Butyl Ester

収率 61.0%

溶媒

THF

dichloromethane

isopropanol

THF

反応条件

後処理

1. 1
   workup.STIRRINGto stir at −40° C. for 15 minutes
2. 2
   温度The reaction mixture was warmed up to room temperature
3. 3
   その他The organic layer was separated
4. 4
   抽出the aqueous layer was extracted with 3×30 mL of dichloromethane
5. 5
   乾燥dried (anhydrous Na2SO4)
6. 6
   濃縮concentrated under reduced pressure
7. 7
   その他The residue was purified by silica gel flash column chromatography

実験手順

A solution of 200 μL (2.3 mmol) of ethynyl-cyclopropane in 2 mL of freshly distilled THF was cooled to −40° C. and 1 mL (2.5 mmol) of n-butyl lithium (2.5M in hexane) was added under argon atmosphere. The reaction mixture was allowed to stir at −40° C. for 10 minutes. To the reaction mixture a solution of 400 mg (1.0 mmol) of 6 in 4 mL of freshly distilled THF was added, and the reaction was allowed to stir at −40° C. for 15 minutes. To the reaction mixture 2 mL of isopropanol were added followed by 20 mL of saturated ammonium chloride solution at −40° C. The reaction mixture was warmed up to room temperature, and 30 mL of dichloromethane was added. The organic layer was separated, and the aqueous layer was extracted with 3×30 mL of dichloromethane. The organic layers were combined, dried (anhydrous Na2SO4), and concentrated under reduced pressure. The residue was purified by silica gel flash column chromatography using 20% ethyl acetate in hexane to give 280 mg (0.61 mmol, 60%) of 7 [LC-MS; M+Na 482.2].

出典