Reaktion #453668

Reaktionsgleichung

methanol

4-benzyloxycarbonyl-1-(4-[5-fluoro-1-(2-trimethylsilylethane-sulfonyl)indol-3-yl]piperidine-1-sulfonyl)piperazine-2-(RS)-carboxylic acid

oxalyl chloride

hydroxylamine

→

piperazine-2-(RS)-carboxamide

Lösungsmittel

methylene chloride

Reaktionsbedingungen

Aufarbeitung

1. 1
   EinengenThe reaction mixture was concentrated in vacua
2. 2
   workup.DISSOLUTIONredissolved in methylene chloride (5 ml)
3. 3
   Temperaturcooled to 0° C
4. 4
   Temperaturthe reaction was warmed to RT
5. 5
   workup.WAITstred for 3 h
6. 6
   Sonstigerecooled to 0° C
7. 7
   workup.STIRRINGthe mixture was stirred for an additional 30 min.
8. 8
   Einengenconcentrated in vacuo
9. 9
   SonstigeThe residue was partitioned between methylene chloride (50 ml) and aqueous 2.4 M HCl (10 ml)
10. 10
    Sonstigethe organic layer was separated
11. 11
    Waschenwashed with saturated aqueous sodium bicarbonate
12. 12
    Trocknendried over MgSO4
13. 13
    Einengenconcentrated in vacuo

Vorschrift

To a solution of 4-benzyloxycarbonyl-1-(4-[5-fluoro-1-(2-trimethylsilylethane-sulfonyl)indol-3-yl]piperidine-1-sulfonyl)piperazine-2-(RS)-carboxylic acid(288 mg, 0.40 mmol), [prepared as described in Step 6 above] in methylene chloride (5 ml) at 0° C. were added a few drops of DMF and oxalyl chloride (89 ml, 1.0 mmol). The reaction mixture was warmed to RT over 1 h, and stirring was continued for an additional 14 h. The reaction mixture was concentrated in vacua, redissolved in methylene chloride (5 ml) and cooled to 0° C. N,O-bis-trithylsilyl hydroxylamine (0.304 ml, 1.42 mmol) added, the reaction was warmed to RT, stred for 3 h, and then recooled to 0° C. After adding methanol (3 ml), the mixture was stirred for an additional 30 min., and then concentrated in vacuo. The residue was partitioned between methylene chloride (50 ml) and aqueous 2.4 M HCl (10 ml), the organic layer was separated and washed with saturated aqueous sodium bicarbonate, dried over MgSO4, and concentrated in vacuo to afford N-hydroxy-4-benzyloxycarbonyl-1-j4-[5-fluoro-1-2-trmethylsilylethanesulfonyl)-indol-3-yl]-piperidine-1-sulfonyl ) piperazine-2-(RS)-carboxamide as a yellow foam (250 mg, 86%). The residue was used without further purification.

Quelle