反応 #48627

反応方程式

benzyl bromide

sodium hydride

benzyl bromide

4-(R)-[2-(S)-amino-1-(S)-hydroxy-3-(3-hydroxyphenyl)-propyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester

sodium hydride

→

desired compound

4-(R)-[1-(S)-benzyloxy-3-(3-benzyloxyphenyl)-2-(S)-dibenzylaminopropyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester

溶媒

ethyl acetate

tetrahydrofuran

tetrahydrofuran

反応条件

後処理

1. 1
   濃縮concentrate
2. 2
   workup.STIRRINGstir overnight at 65° C
3. 3
   その他quench with water (300 mL)
4. 4
   洗浄wash with water, and saturated aqueous sodium chloride
5. 5
   抽出Extract the aqueous washes with ethyl acetate
6. 6
   乾燥dry (magnesium sulfate)
7. 7
   ろ過filter
8. 8
   その他purify twice
9. 9
   洗浄(silica gel chromatography, eluting with 5:95 to 10:90 ethyl acetate:hexanes)

実験手順

Add tricaprylmethylammonium chloride (Aliquat® 336) (4.5 g, 11.2 mmol) and tetrabutylammonium bromide (TBAB) (5.7 g, 15.7 mmol) to a solution of 4-(R)-[2-(S)-amino-1-(S)-hydroxy-3-(3-hydroxyphenyl)-propyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester (16.45 g, crude) in tetrahydrofuran (200 mL). Add portionwise 95% sodium hydride (2.6 g, 90 mmol) and stir for 10 minutes. Add benzyl bromide (13.4 mL, 112.5 mmol) and heat at 60° C. for 40 minutes and concentrate. Add more 95% sodium hydride (5.4 g, 225 mmol) and benzyl bromide (27 mL, 225 mmol) in tetrahydrofuran (−5 mL) and stir overnight at 65° C. Dilute with ethyl acetate, quench with water (300 mL), wash with water, and saturated aqueous sodium chloride. Extract the aqueous washes with ethyl acetate, comvine the organic layers, dry (magnesium sulfate), filter and purify twice (silica gel chromatography, eluting with 5:95 to 10:90 ethyl acetate:hexanes) to give the desired compound as an orange residue (16.01 g, 49%).

出典