反応 #220119

反応方程式

tert-butyl 2-formylpiperidine-1-carboxylate

(2R,4R)-4-(allyloxy)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid

( 3 )

(2R,4R)-tert-butyl 4-(allyloxy)-2-(hydroxymethyl)pyrrolidine-1-carboxylate

tert-butyl 2-((1S,2S)-2-(3,5-difluorobenzyl)-3-((S)-4-benzyl-2-oxooxazolidin-3-yl)-1-hydroxy-3-oxopropyl)piperidine-1-carboxylate

(S)-4-benzyl-3-(3-(3,5-difluorophenyl)propanoyl)oxazolidin-2-one

Bu2BOTf

triethyl amine

→

title compound

(1S,2S)-2-amino-1-((R)-1-benzhydrylpiperidin-2-yl)-3-(3,5-difluorophenyl)propan-1-ol

溶媒

CH2Cl2

MeOH

CH2Cl2

反応条件

後処理

1. 1
   その他was brought up to 0° C.
2. 2
   workup.ADDITIONWhen the addition
3. 3
   温度to warm to and
4. 4
   workup.STIRRINGstirred at rt overnight
5. 5
   濃縮the mixture was concentrated in vacuo
6. 6
   その他The crude mixture was purified by silica gel Flash chromatography

実験手順

Step I (3): Preparation of tert-butyl 2-((1S,2S)-2-(3,5-difluorobenzyl)-3-((S)-4-benzyl-2-oxooxazolidin-3-yl)-1-hydroxy-3-oxopropyl)piperidine-1-carboxylate. To a solution of (S)-4-benzyl-3-(3-(3,5-difluorophenyl)propanoyl)oxazolidin-2-one (Preparation M, 2.2 g, 6.57 mmol) in CH2Cl2 (100 mL) at −78° C. was added Bu2BOTf (di-n-butylboron triflate) (7.9 ml, 7.9 mmol, 1M in CH2Cl2) and triethyl amine (1.4 mL, 10 mmol). The resulting mixture was brought up to 0° C. and stirred for 20 min. The mixture was cooled back to −78° C. and a solution of tert-butyl 2-formylpiperidine-1-carboxylate (Step I (2), 1.4 g, 6.57 mmol) in CH2Cl2 (100 mL) was added. When the addition was complete, the mixture was allowed to warm to and stirred at rt overnight. MeOH was added and the mixture was concentrated in vacuo. The crude mixture was purified by silica gel Flash chromatography to give 2.0 g of the title compound: 1H NMR (CDCl3, 500 MHz) δ 1.42-1.66 (14H, m), 1.86-2.26 (1H, m), 2.62-3.40 (6H, m), 3.84-4.69 (7H, m), 6.58-6.65 (1H, m), 6.81-6.85 (2H, m), 6.90-6.96 (2H, m), 7.22-7.27 (3H, m). MS (ESI) (M+Na)+ 581.12.

出典