4-Chlorobutyryl chloride

Phosgene (165) or thionyl chloride in the presence of an acid catalyst (166) gives good yields of 4-chlorobutyryl chloride. Heating butyrolactone and thionyl chloride in an alcohol gives good yields of 4-chlorobutyric esters (167). 

Alkylation of the basic amino group in (19-6) with butyrophenone (20-1), available from the acylation of fluorobenzene with 4-chlorobutyryl chloride, affords the antipsychotic drug droperidol (20-2) [21]. Alkylation of the fully reduced intermediate (19-7) with a side chain (20-3) yields pimozide (20-4) [22]. 

The first-generation synthesis of levetiracetam (3), as shown in Scheme 14.9 [29], starts with benzoyl protection and oxidation of (S)-aminobutanol (32), which gives rise to the corresponding N-benzoyl protected (S)-aminobutyric acid (33). After N-benzoyl amidation and deprotection, (S)-aminobutyramide (34) is obtained. Chemoselective butyrolactam ring formation using the intermediate 34 and 4-chlorobutyryl chloride finally affords levetiracetam (3). 

Other experimental conditions can be important.84 Thus the electroreduc-tive coupling between 4-chlorobutyryl chloride and nitrosobenzene to 2-phenyltetrahydro-2H-1,2-oxazine-3-one gives low yields in DMF at room temperature. An acceptable yield is obtained in acetonitrile at room temperature, still more at - 18°C. The lower yield obtained using DMF is due mainly to a higher reactivity of the electrophile, which forms an immonium salt with DMF. 

A. corymbifera LCP 63-1800 Aluminum chloride 4-Chlorobutyryl chloride 4-Piperidinemethanol, a,a-diphenyl-... 

Chlorobutyryl chloride (2.13 mol) was dissolved in 3L THF, 252 ml 2,6-lutidine and 30 g 5% palladium on carbon added, and the mixture hydrogenated while shaking under 60 psi hydrogen 6 hours. Thereafter, the mixture was purged with nitrogen, filtered, and concentrated. The mixture was purified by distillation and 148.3 g product isolated. 

Chlorobutyryl chloride cyc/oButanecarbonyl chloride rerr-Butylacetyl chloride... 

Condensation catalyst [1, 933-934, after citation of ref. 5]. 4-Chlorobutyryl chloride (0.71 mole) when treated with potassium fluoride (2.74 moles) at 195— 200° in tetramethylene sulfone is converted in 70% yield into cyclopropanecarb-oxylic acid fluoride.53 Evidence is presented that the reaction proceeds in two steps, first conversion of the acyl chloride into the fluoride, and then cyclization catalyzed... 

Chloro-2-butene, 290 4-Chlorobutyryl chloride, 346 /3-Chlorocarbamates, 121 Chlorocarbonylbis(triphenylphosphine)-... 

An alternate method started from 5,6-diamino-1,3-dipropyluracil which reacted with 4-chlorobutyryl chloride to give 6-amino-5-(4-chlorobutyryl)amino-1,3-dipropyl- I //,3//-pyrimidine-2,4-dione (17a) and subsequently underwent cyclization in diphenyl ether under reflux. The water produced in this step hydrolyzed the product into 8-(3-hydroxypropyl)-l,3-dipropyl-7/7-purine-2,4(1/7,3/7)-dione (19a). Heating the latter in thionyl chloride led to the appropriate 8-(3-chloropropyl) derivative 19b which underwent intramolecular alkylation with NaOCH3 to afford the final tricyclic 20b. Another route started from 6-amino-5-(4-chlorobutyl)amino derivative 17a by an intramolecular alkylation to 6-amino-5-(2-oxopyrolidin-l-yl)-1,3-dipropyl- 1/7,3/7-pyrimidine-2,4-dione (17b) and its subsequent cyclization by phosphorus oxychloride under reflux to 20b (94JHC81) (Scheme 5). 

An efficient synthesis of iV-ethyl-l-hydroxy-7-methoxymitosane (115) was reported by Verboom and co-workers [39, 40]. This synthesis was based on a variation of the Madelung reaction in which the cyclization to an indole was facilated by an electron-withdrawing cyano group on the benzylic carbon (Scheme 15). The starting material, 2-amino-5-methoxy-4-methylbenzonitrile (110), was treated with 4-chlorobutyryl chloride to give amide 111, which was... 

Chlorobutyryl chloride added with vigorous stirring during 50 min. to dry KF in sulfolane with spontaneous distillation of the product from the exothermic reaction at such a rate that the temp, in the take-off head is kept at 80-100° -> cycloprop anecar boxy lie acid fluoride. Y 70.4%. Also from the 4-bromo analog s. R. E. A. Dear and E. E. Gilbert, J. Org. Chem. 33, 1690 (1968). 

Electrophile 1, benzoyl chloride II, /j-bromobenzoyl chloride III, 4-chlorobutyryl chloride IV, ethyl chloroformate,... 

The second material is a end functionalized cation with trimethylammonium carrying the positive charge. This functionality is similar to that of in-vivo carnitine, which fimction as a complexing carrier for the transport of long chain activated fatty acids into the mitochondrial matrix (6). The second material is prepared in two steps initially 4-chlorobutyryl chloride is reacted onto the cohydroxyl end-group of PTMC, finally trimethylamine displaces the chloride to introduce the cationic ammonium group. 

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