Reaction #81345

ord-6c63a7b0bcdf4386a1182731aa9a9a7e

Reaction equation

CCCCCC.CCOC(C)=O
ethyl acetate hexane
C[C@@H]1C[C@H]2[C@@H]3C[C@H](F)C4=CC(=O)C=C[C@]4(C)[C@H]3[C@@H](O)C[C@]2(C)[C@H]1C(=O)CO
fluocortolone
CC(C)[C@H](NC(=O)OC(C)(C)C)C(=O)O
Boc-valine
C(=NC1CCCCC1)=NC1CCCCC1
dicyclohexylcarbodiimide
→
CC(C)[C@H](NC(=O)OC(C)(C)C)C(=O)OC(O)C(=O)[C@H]1[C@H](C)C[C@H]2[C@@H]3C[C@H](F)C4=CC(=O)C=C[C@]4(C)[C@H]3[C@@H](O)C[C@@]21C
(2S)-2-((1,1-dimethylethoxycarbonyl)-amino)-3-methyl-butyric acid [11β,21-dihydroxy-6α-fluoro-16α-methyl-3,20-dioxo-pregna-1,4-dien-21-yl] ester
Yield 46.0%

Reactants

CCCCCC.CCOC(C)=O
ethyl acetate hexane
C[C@@H]1C[C@H]2[C@@H]3C[C@H](F)C4=CC(=O)C=C[C@]4(C)[C@H]3[C@@H](O)C[C@]2(C)[C@H]1C(=O)CO
fluocortolone
CC(C)[C@H](NC(=O)OC(C)(C)C)C(=O)O
Boc-valine
C(=NC1CCCCC1)=NC1CCCCC1
dicyclohexylcarbodiimide
—
F2
—
F1

Reagents

CN(C)c1ccncc1
4-dimethylaminopyridine

Solvents

C1COCCO1.ClCCl
dichloromethane dioxane

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    Other(Total yield 92%) crystallization of F1 from ethyl acetate/hexane

Procedure

26 mmol of fluocortolone (FC) is reacted with 32 mmol of Boc-valine (Boc-Val-OH), 2.9 mmol of 4-dimethylaminopyridine and 34 mmol of dicyclohexylcarbodiimide in dichloromethane/dioxane 3:2. Chromatography (ethyl acetate/hexane 2:1): F1 9.3 g of pure product, F2 4.8 g of slightly contaminated product. (Total yield 92%) crystallization of F1 from ethyl acetate/hexane yields 7.0 g (46%) of (2S)-2-((1,1-dimethylethoxycarbonyl)-amino)-3-methyl-butyric acid [11β,21-dihydroxy-6α-fluoro-16α-methyl-3,20-dioxo-pregna-1,4-dien-21-yl] ester.

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US05616573uspto-grants-1997_04