e.g. Filippa Pettersson or Cancer Res. 75(6) , 1102-12, (2015) or 10.1002/anie.201600521

Synthesis

Synthesis of (S, R, R, R)-α, α′-Iminobis (methylene) bis (6-fluoro-3H, 4H-dihydro-2H-1-benzopyran-2-methanol)

NX Wang, AG Yu, GX Wang, XH Zhang, QS Li, Z Li

Index: Wang, Nai-Xing; Yu, An-Guang; Wang, Gui-Xia; Zhang, Xiu-Hui; Li, Qian-Shu; Li, Zhen Synthesis, 2007 , # 8 p. 1154 - 1158

Full Text: HTML

Citation Number: 9

Abstract

Abstract The β 1-adrenergic antagonist (S, R, R, R)-α, α′-iminobis (methylene) bis (6-fluoro- 3H, 4H-dihydro-2H-1-benzopyran-2-methanol) was synthesized from natural chiral pool starting materials through an efficient, convergent synthetic strategy. The cyclization mechanism of the key step was investigated using computer modeling and is discussed.

(1’R,2S)-2-[(1’,2’-O-Isopropylidene)dihydroxyethyl]-6-fluorochroman-4-one Structure

(1’R,2S)-2-[(1’...

~60%

(1’R,2S)-2-(1’,2’-Dihydroxyethyl)-6-fluorochromane Structure

(1’R,2S)-2-(1’,...

Tosyl chloride Structure

(1’R,2S)-2-(1’,2’-Dihydroxyethyl)-6-fluorochromane Structure

(1’R,2S)-2-(1’,...

~87%

(1’R,2S)-2-(2’-Tosyl-1’,2’-dihydroxyethyl)-6-fluorochromane Structure

(1’R,2S)-2-(2’-...

5′-Fluoro-2′-hydroxyacetophenone Structure

5′-Fluoro-2′-hy...

~%

(1’R,2S)-2-(2’-Tosyl-1’,2’-dihydroxyethyl)-6-fluorochromane Structure

(1’R,2S)-2-(2’-...

(1’R,2S)-2-[(1’,2’-O-Isopropylidene)dihydroxyethyl]-6-fluorochroman-4-one Structure

(1’R,2S)-2-[(1’...

~%

(1’R,2S)-2-(2’-Tosyl-1’,2’-dihydroxyethyl)-6-fluorochromane Structure

(1’R,2S)-2-(2’-...

4-Fluorophenol Structure

~%

(1’R,2R)-2-[(1’,2’-O-Isopropylidene)dihydroxyethyl]-6-fluorochroman-4-one Structure

(1’R,2R)-2-[(1’...

1,2:5,6-Bis-O-(1-methylethylidene)-D-mannitol Structure

1,2:5,6-Bis-O-(...

~%

(1’R,2R)-2-[(1’,2’-O-Isopropylidene)dihydroxyethyl]-6-fluorochroman-4-one Structure

(1’R,2R)-2-[(1’...

5′-Fluoro-2′-hydroxyacetophenone Structure

5′-Fluoro-2′-hy...

(R)-(+)-2,2-Dimethyl-1,3-dioxolane-4-carboxaldehyde Structure

(R)-(+)-2,2-Dim...

~16%

(1’R,2S)-2-[(1’,2’-O-Isopropylidene)dihydroxyethyl]-6-fluorochroman-4-one Structure

(1’R,2S)-2-[(1’...

(1’R,2R)-2-[(1’,2’-O-Isopropylidene)dihydroxyethyl]-6-fluorochroman-4-one Structure

(1’R,2R)-2-[(1’...

4-Fluorophenol Structure

~%

(1’R,2S)-2-[(1’,2’-O-Isopropylidene)dihydroxyethyl]-6-fluorochroman-4-one Structure

(1’R,2S)-2-[(1’...

1,2:5,6-Bis-O-(1-methylethylidene)-D-mannitol Structure

1,2:5,6-Bis-O-(...

~%

(1’R,2S)-2-[(1’,2’-O-Isopropylidene)dihydroxyethyl]-6-fluorochroman-4-one Structure

(1’R,2S)-2-[(1’...

5′-Fluoro-2′-hydroxyacetophenone Structure

5′-Fluoro-2′-hy...

(R)-(+)-2,2-Dimethyl-1,3-dioxolane-4-carboxaldehyde Structure

(R)-(+)-2,2-Dim...

~24%

(1’R,2S)-2-[(1’,2’-O-Isopropylidene)dihydroxyethyl]-6-fluorochroman-4-one Structure

(1’R,2S)-2-[(1’...

(1’R,2R)-2-[(1’,2’-O-Isopropylidene)dihydroxyethyl]-6-fluorochroman-4-one Structure

(1’R,2R)-2-[(1’...

Tosyl chloride Structure

(1’R,2R)-2-(1’,2’-Dihydroxyethyl)-6-fluorochromane Structure

(1’R,2R)-2-(1’,...

~77%

(1’R,2R)-2-(2’-Tosyl-1’,2’-dihydroxyethyl)-6-fluorochromane Structure

(1’R,2R)-2-(2’-...

5′-Fluoro-2′-hydroxyacetophenone Structure

5′-Fluoro-2′-hy...

~%

(1’R,2R)-2-(2’-Tosyl-1’,2’-dihydroxyethyl)-6-fluorochromane Structure

(1’R,2R)-2-(2’-...

(1’R,2R)-2-[(1’,2’-O-Isopropylidene)dihydroxyethyl]-6-fluorochroman-4-one Structure

(1’R,2R)-2-[(1’...

~%

(1’R,2R)-2-(2’-Tosyl-1’,2’-dihydroxyethyl)-6-fluorochromane Structure

(1’R,2R)-2-(2’-...