Reaction #81343

ord-a60f758833af4ae5911eeed9ebfd2328

Reaction equation

C[C@]12CCC(=O)C=C1CC[C@@H]1[C@@H]2[C@@H](O)C[C@@]2(C)[C@H]1CC[C@]2(O)C(=O)CO
hydrocortisone
CC(C)[C@H](NC(=O)OC(C)(C)C)C(=O)O
N-(tert -butoxycarbonyl)-valine
C(=NC1CCCCC1)=NC1CCCCC1
dicyclohexylcarbodiimide
→
CC(C)[C@H](NC(=O)OC(C)(C)C)C(=O)OC(O)C(=O)[C@@]1(O)CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)[C@H]3[C@@H](O)C[C@@]21C
(2S)-2-((1,1-dimethylethoxycarbonyl)-amino)-3-methylbutyric acid [11β,17,21-trihydroxy-3,20-dioxo-pregn-4-en-21-yl] ester
Yield 51.0%

Reactants

C[C@]12CCC(=O)C=C1CC[C@@H]1[C@@H]2[C@@H](O)C[C@@]2(C)[C@H]1CC[C@]2(O)C(=O)CO
hydrocortisone
CC(C)[C@H](NC(=O)OC(C)(C)C)C(=O)O
N-(tert -butoxycarbonyl)-valine
C(=NC1CCCCC1)=NC1CCCCC1
dicyclohexylcarbodiimide

Reagents

CN(C)c1ccncc1
4-dimethylaminopyridine

Solvents

ClCCl
dichloromethane

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    Otherthe precipitate that is produced
  2. 2
    Washwashed with dichloromethane
  3. 3
    ConcentrationThe filtrate is concentrated by evaporation in a vacuum

Procedure

A solution of 3.63 g (10 mmol) of hydrocortisone in 150 ml of dichloromethane is mixed with 2.34 g (10.8 mmol) of N-(tert -butoxycarbonyl)-valine, 500 mg (4.1 mmol) of 4-dimethylaminopyridine and 3.1 g (15 mmol) of dicyclohexylcarbodiimide. The solution is stirred for 3 hours at room temperature, the precipitate that is produced is suctioned off and washed with dichloromethane. The filtrate is concentrated by evaporation in a vacuum. The chromatography on silica gel (hexane→hexane/ethyl acetate 1:1) provides 2.87 g (51%) of (2S)-2-((1,1-dimethylethoxycarbonyl)-amino)-3-methylbutyric acid [11β,17,21-trihydroxy-3,20-dioxo-pregn-4-en-21-yl] ester. Crystallization from dichloromethane/diisopropyl ether.

Source

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