Pivaloyl chloride → N-(N-(N-(N-(2,2-dimethylpropionyl)-L-alanyl)-L-alanyl)-L-prolyl)-L-valine [11beta,21-dihydroxy-3,20-dioxo-6alpha-methyl-17-propionyloxy-pregna-1,4-dien-21-yl] ester

HRID 53064Notes

Reaction equation

HRID 53064 reaction equation
[OH:1][C@H:2]1[CH2:54][C@@:53]2([CH3:55])[C@@H:13]([CH2:14][CH2:15][C@:16]2([O:56][C:57](=[O:60])[CH2:58][CH3:59])[C:17](=[O:52])[CH:18]([O:20][C:21](=[O:51])[C@H:22]([CH:48]([CH3:50])[CH3:49])[NH:23][C:24](=[O:47])[C@@H:25]2[CH2:29][CH2:28][CH2:27][N:26]2[C:30](=[O:46])[C@H:31]([CH3:45])[NH:32][C:33](=[O:44])[C@H:34]([CH3:43])[NH:35]C(OC(C)(C)C)=O)[OH:19])[C@H:12]2[C@H:3]1[C@:4]1([CH3:63])[C:9]([C@@H:10]([CH3:61])[CH2:11]2)=[CH:8][C:7](=[O:62])[CH:6]=[CH:5]1.C(N(C(C)C)CC)(C)C.[C:73](Cl)(=[O:78])[C:74]([CH3:77])([CH3:76])[CH3:75]>ClCCl>[OH:1][C@H:2]1[CH2:54][C@@:53]2([CH3:55])[C@@H:13]([CH2:14][CH2:15][C@:16]2([O:56][C:57](=[O:60])[CH2:58][CH3:59])[C:17](=[O:52])[CH:18]([O:20][C:21](=[O:51])[C@H:22]([CH:48]([CH3:49])[CH3:50])[NH:23][C:24](=[O:47])[C@@H:25]2[CH2:29][CH2:28][CH2:27][N:26]2[C:30](=[O:46])[C@H:31]([CH3:45])[NH:32][C:33](=[O:44])[C@H:34]([CH3:43])[NH:35][C:73](=[O:78])[C:74]([CH3:77])([CH3:76])[CH3:75])[OH:19])[C@H:12]2[C@H:3]1[C@:4]1([CH3:63])[C:9]([C@@H:10]([CH3:61])[CH2:11]2)=[CH:8][C:7](=[O:62])[CH:6]=[CH:5]1

Participants

5

Reactant 3

HCID 62493Pivaloyl chlorideHCID 81531DiisopropylethylamineHCID 131719958N-(N-(N-(N-(1,1-Dimethylethoxycarbonyl)-L-alanyl)-L-alanyl)-L-prolyl)-L-valine [11beta,21-dihydroxy-3,20-dioxo-6alpha-methyl-17-propionyloxy-pregna-1,4-dien-21-yl] ester

Product 1

HCID 131719961N-(N-(N-(N-(2,2-dimethylpropionyl)-L-alanyl)-L-alanyl)-L-prolyl)-L-valine [11beta,21-dihydroxy-3,20-dioxo-6alpha-methyl-17-propionyloxy-pregna-1,4-dien-21-yl] ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

150 mg (0.17 mmol) of H-Ala-Ala-Pro-Val-O-MPP x TFA (Example 3) and 60 μl (0.34 mmol) of diisopropylethylamine are dissolved in 6 ml of dichloromethane, mixed with 20 μl (0.18 mmol) of pivaloyl chloride and stirred for 25 hours at room temperature. The residue that remains after removal of the solvent i.vac. is directly chromatographed. Gradient chromatography (24 g of silica gel 60, hexane→hexane/acetone 7:3) yields 102 mg (70%) of slightly contaminated N-(N-(N-(N-(2,2-dimethylpropionyl)-L -alanyl)-L-alanyl)-L-prolyl)-L-valine [11β,21-dihydroxy-3,20-dioxo-6α-methyl-17-propionyloxy-pregna-1,4-dien-21-yl] ester. A second chromatography (Lichroprep Si60A pre-packed column, hexane/dichloromethane 1:1→hexane/dichloromethane/methanol 30:60:10) yields 92 mg, 83 mg of crystalline compound consisting of dichloromethane/diisopropyl ether.

Workup

  1. customafter removal of the solvent i.vac
  2. customis directly chromatographed

Sources & evidence

ORD record
ord-e90c8f0ff2f14aa5b32c43e2524a322c
Source dataset
uspto-grants-1997_04
Patent number
US05616573

Reaction notes

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