反応 #1973910

反応方程式

3-bromo-2-hydroxycyclohex-1-enecarboxylic acid ethyl ester

3-Bromo-2-hydroxy-cyclohex-1-enecarboxylic acid ethyl ester

potassium bis(trimethylsilyl) amide

(2-Benzyloxy-ethyl)-(2-chloro-5-methoxyphenyl) amine

Acetic acid

→

3[(2-Benzyloxy-ethyl)-(2-chloro-5-methoxy-phenyl)-amino]-2-hydroxy-cyclohex-1-ene carboxylic acid ethyl ester

収率 104.9%

溶媒

THF

toluene

THF

反応条件

後処理

1. 1
   濃縮concentrated in vacuo
2. 2
   その他to remove the THF
3. 3
   workup.ADDITIONEthyl acetate (200 mL) and 10% aqueous potassium carbonate (100 mL) was added
4. 4
   その他The ethyl acetate solution was separated
5. 5
   乾燥dried over magnesium sulfate
6. 6
   濃縮concentrated in vacuo

実験手順

(2-Benzyloxy-ethyl)-(2-chloro-5-methoxyphenyl) amine (3) (10.0 g, 34.2 mmol) was stirred in dry THF (100 mL) at −40° C. under nitrogen and potassium bis(trimethylsilyl) amide (143.0 mL of a 0.5 M solution in toluene, 72.0 mmol) was added over 30 min. 3-bromo-2-hydroxycyclohex-1-enecarboxylic acid ethyl ester (4) (8.5 g, 34.2 mmol) in dry THF (10 mL) was then added and allowed to warm to RT over a period of 1.5 h. Acetic acid (10.0 g, 166 mmol, 10.0 mL) was added and concentrated in vacuo to remove the THF. Ethyl acetate (200 mL) and 10% aqueous potassium carbonate (100 mL) was added and the mixture vigorously shaken. The ethyl acetate solution was separated, dried over magnesium sulfate and concentrated in vacuo to afford 16.5 g (quantitative) of 3[(2-Benzyloxy-ethyl)-(2-chloro-5-methoxy-phenyl)-amino]-2-hydroxy-cyclohex-1-ene carboxylic acid ethyl ester (5) as a gum which was used crude in the next step. HPLC (Gemini 150×4.6 mm, 50-95% methanol/water over 20 min) of crude reaction mixture, 18.9 min (38%), 19.2 min (25%), 23.1 min (28%).

出典