Synthesis of carboxy‐¹⁴C furosemide

Abstract

A . A. L i e b m a n , A. M . D o r s k y and D. H. M a l a r e k C h e m i c a l R e s e a r c h D e p a r t m e n t , H o f f m a n n -L a R o c h e Inc., N u t l e y , N. J. 0 7 1 1 0 , U. S. A. R e c e i v e d o n M a r c h 6, 1974. SUMMARY A modification of the Sandmeyer reaction which requires only a moderate excess of ~yanide-'~C was utilized for the preparation of 4-chloro-2-fluorobenzonitriZe-7-C (a. After hydrolysis, the resulting acid (a was converted to carboxg labelled furosemide (u by existing methods. useful for insertion of I4C in compounds that fail to undergo conventional carbonation reactions.14 This procedure is potentially

Synthesis of the Pentacyclic Skeleton of the Aspidosperma Alkaloids Using Rhodium Carbenoids as Reactive Intermediates

“…Our synthesis of the required diazo imide 12 commences with the easily available 3-carboxy-3-ethyl-2piperidone (27). 26 Treatment of 27 with 1,1-carbonyldiimidazole followed by reaction with the dianion of hydrogen methyl malonate 27 afforded β-keto ester 14 in 60% yield (Scheme 3). N-Acylation of 14 with N-methylindole-3-acetyl chloride (13) using 4 Å molecular sieves as a neutral acid scavenger 28 gave the desired imide (65%) which was readily converted to the requisite diazo imide 12 using standard diazo transfer methodology.…”

“…To 50 mg (0.1 mmol) of 25 in 0.5 mL of benzene was added 2 mg of rhodium(II) acetate. The mixture was heated to 50 °C in an oil bath for 3 h and concentrated under reduced pressure, and the residue was subjected to flash silica gel chromatography to give 0.40 g (90%) of 3,18-dicarbethoxy-3,19-epoxy-4,10-dioxo-1-methylaspidospermidine (26) 3-Carboxy-3-ethyl-2-piperidone (27). To a 68 g (36 mmol) sample of diethyl ethylmalonate in 300 mL of a 1:1 THF:DME solution was added 100 g (72 mmol) of K 2CO3.…”

6,7-Benzomorphans. Stereospecific synthesis of 2,9.alpha.- and 2,9.beta.-dimethyl-2'-methoxy-6,7-benzomorphans

“…Caled for Ci4H21NO: C, 76.7; H, 9.7; N, 6.4. Found: C, 77.0; H, 9.7; N, 6.3. trans-l,3-Dimethyl-4-(3-methoxyphenyl)piperidine (45). irans-Amine 45 was prepared by L1AIH4 reduction of irons-piperidone 43 in a manner analogous to that for 42 followed by separation by GC (column B, 140 °C) or more conveniently by DIBAL reduction of nitrile 47.…”

A simple and practical synthesis of olivetol

“…This sequence has also been used to incorporate a labeled carbon atom in the aromatic ring. 19 The alternative route leads to a variety of intermediates which per se could be of synthetic interest. The keto-enol 4, used originally by adams20 and co-workers in the synthesis of cannabinol, was laboriously prepared by partial reduction of olivetol.…”