Ammonium Chloride → Ethyl 4-(cyclopropanesulfonamido)-2-ethyl-1-fluorocyclopentanecarboxylate

Temperatur

-78 °C

A solution of ethyl 4-(cyclopropanesulfonamido)-2-ethylcyclopentanecarboxylate (0.630 g, 2.18 mmol, prepared using K from Preparation #Y.1 and cyclopropanesulfonyl chloride) in THF (14.5 mL) was cooled to about −78° C. and then LDA (1.8 M in THF/hexane, 3.63 mL, 6.53 mmol) was added dropwise to the reaction mixture over about 30 min. The reaction mixture was stirred at about −78° C. for about 50 min before a solution of N-fluoro-N-(phenylsulfonyl)benzenesulfonamide (2.06 g, 6.53 mmol) in THF (7.3 mL) was added dropwise over about 30 min. The reaction mixture was stirred at about −78° C. for about 1 h and then was warmed to ambient temperature and stirred for about 16 h. Saturated aqueous NH4Cl (100 mL) was added. The reaction mixture was partitioned with EtOAc (50 mL). The aqueous layer was further extracted with EtOAc (2×50 mL). The combined organic layers were concd under reduced pressure. The residue was purified by silica gel chromatography eluting with a gradient of 0-60% EtOAc in heptane to yield ethyl 4-(cyclopropanesulfonamido)-2-ethyl-1-fluorocyclopentanecarboxylate (0.41 g, 46%) as clear oil: LC/MS (Table 1, Method b) Rt=2.12 min; MS m/z: 306 (M−H)−.

1. additionwas added dropwise over about 30 min
2. temperaturewas warmed to ambient temperature
3. stirringstirred for about 16 h
4. customThe reaction mixture was partitioned with EtOAc (50 mL)
5. extractionThe aqueous layer was further extracted with EtOAc (2×50 mL)
6. customThe residue was purified by silica gel chromatography
7. washeluting with a gradient of 0-60% EtOAc in heptane

ORD-Eintrag

ord-34922c24e1294ee0bbcf97b20c159c83

Quelldatensatz

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08426411B2