Diethyl 4-chlorobutanal

The key Fisher indole synthesis using diethyl 4-chlorobutanal (8) suffered from poor yield to make the primary tryptamine 10, which then calls for reductive amination to complete the synthesis. 

We envisioned that improvement of the key Fisher indole reaction using diethyl 4-(N,N-dimethylamino)butanal (11) instead of diethyl 4-chlorobutanal (8) would lead to formation of the desired product directly. The approach would circumvent... 

Amino acid-modified furocoumarins were prepared by condensation of the T-hydroxysuccinimide ester of 3-(2,3,5-trimethyl-7-oxofuro[3,2-g]chromen-6-yl)propanoic acid 51 with amino acids <2003JPH177>. Ethyl 3-(7-hydroxy-4-methyl-2-oxo-2/7-3-chromenyl)propanoate 49, prepared in 56% yield by Pechmann condensation of resorcinol and diethyl 2-acetylglutarate in the presence of HCl, was condensed with 3-chlorobutan-2-one in the presence of base to give propanoate 50 (Scheme 4). The MacLeod method was then used to fuse a furan ring to the benzopyran-2-one system. Heating 50 with NaOH solution (1 M) readily cyclized it into the corresponding psoralen furocoumarin 51 with simultaneous hydrolysis of the ester. 

Almotnptan (5, LAS-31416) was discovered and developed by Almirall in Spain. The U.S. marketing rights were licensed to Pharmacia and then to Janssen. The synthesis commenced with the reaction of (p-nitrophenyl)-methanesulfonyl chloride (57) with pyrrolidine, followed by hydrogenation of the nitro group to give aniline 58 (Scheme 21). The hydrazine 59 was prepared by diazotization of 58 followed by reduction of the resulting diazonium salt with stannous chloride. Hydrazine 59 was treated with 4-chlorobutanal diethyl acetal in aqueous HCl and hydrazone 60 precipitated and was... 

Chlorobenzene Chlorobutane, 1-Chloroform Cyclohexane Diethyl ether Ethanol... 

P-Glucoronidase and extraction with 1 -chlorobutane-diethyl ether and 1-chloro-3-iodopropane GC-MS-MS... 

Alkyl chlorides are strikingly unreactive toward organoalkalis. At +25 C, 1-chlorobutane and -butyllithium, both 0.5 M, show half-survival periods that largely exceed 100 h, in paraffinic or aromatic hydrocarbons, and that still approximate 40 h in diethyl ether. This inertness is of course fortunate as it enables the efficacious preparation of alkyllithiums and alkylsodiums by allowing the reaction of alkyl halides with finely dispersed and hence activated metals to be executed in paraffinic media such as pentanes or hexanes. 

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