Sodium borohydride acyl chlorides

Isoquinoline can be reduced quantitatively over platinum in acidic media to a mixture of i j -decahydroisoquinoline [2744-08-3] and /n j -decahydroisoquinoline [2744-09-4] (32). Hydrogenation with platinum oxide in strong acid, but under mild conditions, selectively reduces the benzene ring and leads to a 90% yield of 5,6,7,8-tetrahydroisoquinoline [36556-06-6] (32,33). Sodium hydride, in dipolar aprotic solvents like hexamethylphosphoric triamide, reduces isoquinoline in quantitative yield to the sodium adduct [81045-34-3] (25) (152). The adduct reacts with acid chlorides or anhydrides to give N-acyl derivatives which are converted to 4-substituted 1,2-dihydroisoquinolines. Sodium borohydride and carboxylic acids combine to provide a one-step reduction—alkylation (35). Sodium cyanoborohydride reduces isoquinoline under similar conditions without N-alkylation to give... 

Reduction of the imine with sodium borohydride leads to an intermediate amino-ester that cyclizes spontaneously to the <5-lactam function. Solvolysis of the acetyl group with methoxide followed by acylation of the hydroxyl group thus liberated with trimethoxybenzoyl chloride leads to 38. Bischler-Napieralski cyclodehydration (phosphorus oxychloride) effects closure of the remaining ring. Reduction of the imine thus formed with sodium borohydride gives 39. This, it should be noted, leads to the... 

In a similar vein, acylation of the corticoid 50 with furoyl chloride gives the diacyl derivative 51. Reduction with sodium borohydride serves to convert the 11-ketone to the alcohol 52. Hydrolysis under mild acid conditions preferentially removes the acyl group at the less hindered 21 position. The hydroxyl group in that derivative (53) is then converted to the mesylate 54. Replacement by chlorine affords mometasone (55) [12]. 

Acylation of 14 with cyclobutylcarbonyl chloride followed by the same series of transformations as above leads to intermediate 22. Reduction of the carbonyl group in that molecule with sodium borohydride gives the analgesic agonist/antagonist nalbuphine (23). 7... 

Reduction of cuprous chloride with sodium borohydride gives copper hydride which is a highly selective agent for the preparation of aldehydes from acyl chlorides [775]. 

Another hydride for the preparation of aldehydes from acyl chlorides is obtained by treatment of a mixture of cuprous chloride and triphenylphos-phine, trimethyl phosphite or triisopropyl phosphite in chloroform with an ethanolic solution of sodium borohydride. Such reagents reduce acyl chlorides to aldehydes in acetone solutions at room temperature in 15-90 minutes in yields ranging from 57% to 83% [115],... 

High yields (76-81%) of alcohols are also obtained by adding solutions of acyl chlorides in anhydrous dioxane or diethyl carbitol to a suspension of sodium borohydride in dioxane and brief heating of the mixtures on the steam bath [751], by stirring solutions of acyl chlorides in ether for 2-4 hours at room temperature with aluminum oxide (activity I) impregnated with a 50% aqueous solution of sodium borohydride (Alox) (yields 80-90%) [1014], by refluxing acyl chlorides with ether solutions of sodium trimethoxyborohydride [99], or by treatment of acyl chlorides in dichloromethane solutions with tetrabutylammonium borohydride at —78° [771]. A 94% yield of neopentyl alcohol was achieved by the reaction of trimethylacetyl chloride with tert-butylmagnesium chloride [324]. 

Thus, treatment of the benzamide (35-1) from 2-phenethylamine with phosphorus oxychloride probably results in an initial formation of a transient enol chloride this then cycUzes to (35-2) under reaction conditions. The imine is then reduced with sodium borohydride. Resolution by means of the tartrate salt affords (35-3) in optically pure form. Acylation of that intermediate with ethyl chloroformate leads to carbamate (35-4). Reaction of this last with the anion from chiral quiniclidol (35-5) interestingly results in the equivalent of an ester interchange. There is thus obtained the anticholinergic agent solifenacin (35-6) [40]. 

The use of activated anthranihc acid derivatives facUitates the preparation of the amides in those cases where the amines are either umeactive or difficult to obtain. Thus, reaction of (87-1) with phosgene gives the reactive the isatoic anhydride (89-1). Condensation of that with ortho-toluidine leads to the acylation product (89-2) formed with a simultaneous loss of carbon dioxide. This is then converted to the quinazolone (89-3) by heating with acetic anhydride. Reaction with sodium borohydride in the presence of aluminum chloride selectively reduces the double bond to yield the diuretic agent metolazone (89-4) [99]. 

Ruoho and Rong have descnbed a shorter route to salmeterol (Scheme 4). Friedel-Crafts acylation of salicylaldehyde (16) with bromoacetyl bromide in the presence of aluminum chloride gave the acetophenone 17. Alkylation of amine 18 with bromoacetyl 17 in refluxing acetonitrile gave the ketone 19. Reduction of 19 with sodium borohydride in methanol followed by catalytic hydrogenolysis of the benzyl group over 10% Pd/C gave salmeterol (2). 

Reduction of RCOCI to RCHO. Sodium borohydride and this cadmium salt reduce acyl chlorides to aldehydes, but only in solvents such as DMF, DMA, and HMPT. DMF is essential, but the amount of DMF in the salt is sufficient. For the most part, yields are 50-90%. Aryl, alkyl, and benzylic halides do not react. Other functional groups (nitrile, nitro, ester, C=C) are also inert. 

From reduction of carboxylic acids and acyl derivatives Sodium borohydride, 278 Sodium cyanoborohydride-Tin(II) chloride, 280... 

The 6-oxopyrido[l,2-a] pyrimidine remained unchanged on catalytic hydrogenation (PtOz, Raney nickel) but decomposed when treated with lithium aluminum hydride.255 The oxo group of the 6-oxo-9a-phenylpyrido-[l,2-a]pyrimidine (179) was reduced with lithium aluminum hydride.230,232 On reduction with sodium borohydride, the 2-phenylpyrido[l,2-a]pyrimi-dine (184) gave the piperidine derivative (182).240,241 The 6-oxoperhydro-pyrido[ 1,2-a]pyrimidines were acylated at the N-l atom with dichloroacetyl chloride.343... 

Dihydrothieno[2,3-6][l,5]benzothiazepines (42) were synthesized from 2-(2-thienylthio)aniline (40). Compound 40 was acylated by treatment with acetic anhydride or benzoyl chloride to give N-acyl derivatives (41), which afforded compounds 42 by cyclization with phosphorus oxychloride and subsequent reduction with sodium borohydride or Zn/HCl. N-Dimethylaminopropyl derivatives 43 were prepared by reaction with di-methylaminopropyl chloride in the presence of sodium amide (Scheme 13) (67CZP124935 68CCC1846). 

Substitution for PABA in a FA analogue by an indole ring has been accomplished by a Russian group Scheme 3.159) [290], Thus, acylation of dimethyl glutamate with 5-nitroindole-2-carbonyl chloride followed by catalytic hydrogenation furnished (701) which was condensed with (11) to yield imine (702). This was reduced with sodium borohydride to give (703) uneventfully. 

There are a number of synthetic routes available to access the benzhy-drols needed for this approach. The first published route to SNC80 used a Friedel-Crafts acylation of toluene with m-anisoyl chloride to yield a benzo-phenone, followed by sodium borohydride reduction of the ketone (after the three-step elaboration of the para-methyl group into the diethylcarboxamide, Scheme 3) [23,24],... 

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