3-Nitrobenzenesulfonyl chloride → N-(cyclopentyloxy)-3-nitro-1-benzenesulfonamide

A mixture of 2-(cyclopentyloxy)-1H-isoindole-1,3(2H)-dione (3.00 g, 12.99 mmol) in anhydrous tetrahydrofuran (25 mL) under an Argon atmosphere was treated with anhydrous hydrazine (0.448 mL, 14.29 mmol). After stirring vigorously for 2.5 hours, the resulting slurry was filtered and washed with approximately 15 mL of anhydrous tetrahydrofuran. The filtrate was combined with 3-nitro-1-benzenesulphonyl chloride (3.17 g, 14.29 mmol) and N,N-diisopropylethylamine (2.72 mL, 15.6 mmol). After stirring at ambient temperature for approximately 18 hours, the reaction mixture was evaporated in vacuo to a residue and partitioned between ethyl acetate and 1N hydrochloric acid. The phases were separated and the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with 5% w/v potassium carbonate and brine, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to a residue. The crude material was purified on flash grade silica gel eluting with 15:85 ethyl acetate:hexane. Fractions containing the product were combined, evaporated in vacuo, and dried under high vacuum to provide N1-(cyclopentyloxy)-3-nitro-1-benzenesulfonamide (3.224 g, 87%) as a solid. H1-NMR (chloroform-D3): 1.71 (m, 8H), 4.71 (m, 1H), 6.93 (bs, 1H), 7.83 (m, 1H), 8.28 (m, 1H), 8.55 (m, 1H), 8.81 (m, 1H).

1. filtrationthe resulting slurry was filtered
2. washwashed with approximately 15 mL of anhydrous tetrahydrofuran
3. stirringAfter stirring at ambient temperature for approximately 18 hours
4. customthe reaction mixture was evaporated in vacuo to a residue
5. custompartitioned between ethyl acetate and 1N hydrochloric acid
6. customThe phases were separated
7. extractionthe aqueous layer was extracted twice with ethyl acetate
8. washThe combined organic layers were washed with 5% w/v potassium carbonate and brine
9. dry with materialdried over anhydrous magnesium sulfate
10. filtrationfiltered
11. customevaporated in vacuo to a residue
12. customThe crude material was purified on flash grade silica gel eluting with 15:85 ethyl acetate
13. additionFractions containing the product
14. customevaporated in vacuo
15. customdried under high vacuum

ORD record

ord-1177d9f1e6e14a019e0045ef9576768c

Source dataset

uspto-grants-2008_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07419967B2