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

温度

-78 °C

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.

1. customwas brought up to 0° C.
2. additionWhen the addition
3. temperatureto warm to and
4. stirringstirred at rt overnight
5. concentrationthe mixture was concentrated in vacuo
6. customThe crude mixture was purified by silica gel Flash chromatography

ORDレコード

ord-f515ed98c4e14f248530b3e0e0c654c8

出典データセット

uspto-grants-2008_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07388007B2