Hydroxylamine → Piperazine-2-carboxamide

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.

1. concentrationThe reaction mixture was concentrated in vacua
2. dissolutionredissolved in methylene chloride (5 ml)
3. temperaturecooled to 0° C
4. temperaturethe reaction was warmed to RT
5. waitstred for 3 h
6. customrecooled to 0° C
7. stirringthe mixture was stirred for an additional 30 min.
8. concentrationconcentrated in vacuo
9. customThe residue was partitioned between methylene chloride (50 ml) and aqueous 2.4 M HCl (10 ml)
10. customthe organic layer was separated
11. washwashed with saturated aqueous sodium bicarbonate
12. dry with materialdried over MgSO4
13. concentrationconcentrated in vacuo

ORDレコード

ord-dc19fbc16a3147b59edf67774d840b2f

出典データセット

uspto-grants-2000_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06130220