Réaction #81347

ord-4aa3a2e7e4c1420a8ea5ecf484c50303

Équation de réaction

CCCCCC.CCOC(C)=O
ethyl acetate hexane
CCCCCC.CCOC(C)=O
ethyl acetate hexane
CCCCC(=O)O[C@]1(C(=O)CO)[C@@H](C)C[C@H]2[C@@H]3CCC4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](O)C[C@@]21C
betamethasone-17-valerate
CC(C)[C@H](NC(=O)OC(C)(C)C)C(=O)O
Boc-valine
→
CCCCC(=O)O[C@]1(C(=O)C(O)OC(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)C)[C@@H](C)C[C@H]2[C@@H]3CCC4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](O)C[C@@]21C
(2S)-2-((1,1-dimethylethoxycarbonyl)-amino)-3-methyl-butyric acid [11β,21-dihydroxy-3,20-dioxo-9-fluoro-16β-methyl-17-valeroyloxy-pregna -1,4-dien-21-yl] ester
Rendement 73.0%

Réactifs

CCCCCC.CCOC(C)=O
ethyl acetate hexane
CCCCCC.CCOC(C)=O
ethyl acetate hexane
CCCCC(=O)O[C@]1(C(=O)CO)[C@@H](C)C[C@H]2[C@@H]3CCC4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](O)C[C@@]21C
betamethasone-17-valerate
CC(C)[C@H](NC(=O)OC(C)(C)C)C(=O)O
Boc-valine

Réactifs

CN(C)c1ccncc1
4-dimethylaminopyridine

Solvants

C1COCCO1.ClCCl
dichloromethane dioxane

Conditions de réaction

Conditions détaillées
See reaction.notes.procedure_details.

Mode opératoire

21 mmol of betamethasone-17-valerate is reacted with 25 mmol of Boc-valine (Boc-Val-OH), 2.5 mmol of 4-dimethylaminopyridine and 27 mmol of dicyclohexylcarbodiimidazole in dichloromethane/dioxane 1:1 analogously to Example 1. Chromatography (1. ethyl acetate/hexane 2:1 and 2. ethyl acetate/hexane 1:1) yields 10.1 g (73%) of pure (2S)-2-((1,1-dimethylethoxycarbonyl)-amino)-3-methyl-butyric acid [11β,21-dihydroxy-3,20-dioxo-9-fluoro-16β-methyl-17-valeroyloxy-pregna -1,4-dien-21-yl] ester as foam.

Source

DOI: 10.6084/m9.figshare.5104873.v1Brevet: US05616573uspto-grants-1997_04