Sodium borohydride acid chlorides

Beccalli et al. reported a new synthesis of staurosporinone (293) from 3-cyano-3-(lH-indol-3-yl)-2-oxo propionic acid ethyl ester (1464) (790). The reaction of 1464 with ethyl chlorocarbonate and triethylamine afforded the compound 1465, which, on treatment with dimethylamine, led to the corresponding hydroxy derivative 1466. The triflate 1467 was prepared from 1466 by reaction with trifluoromethanesulfonic anhydride (Tf20) in the presence of ethyldiisopropylamine. The palladium(O)-catalyzed cross-coupling of the triflate 1467 with the 3-(tributylstannyl)indole 1468 afforded the vinylindole 1469 in 89% yield. Deprotection of both nitrogen atoms with sodium ethoxide in ethanol to 1470, followed by photocyclization in the presence of iodine as the oxidizing agent provided the indolocarbazole 1471. Finally, reductive cyclization of 1471 with sodium borohydride-cobaltous chloride led to staurosporinone (293) in 40% yield (790) (Scheme 5.248). 

The reduction of the nitro group at C-2 of the thiodisacharides was efficiently carried out with sodium borohydride/cobalt chloride complex, followed by conventional acetylation. Final deprotection by ring opening was accomplished by the treatment with p-toluenesulfonic acid in methanol solution followed by deacetylation with aqueous/methanol solution containing catalytic amount of triethylamine. 

Details are now available of the reactions of peracids and of hydrogen peroxide with the imines (10) and (11). The reactions of the product oxaziridines and nitrones with the same two oxidants were also discussed. The reactions of sodium borohydride, benzoyl chloride, and toluene-p-sulphonic acid with the hydroxy-nitrones (12) and (13) have been reported.12 The c.d. spectra of 2-substituted pyrrolidines have been compared with that of conanine (14).13... 

Nicolaou and coworkers have reported an expeditious IBX (2-iodo3gr-benzoic acid, l-hydro q -l, 2-benziodoxol-3(l//)-one 1-oxide) mediated synthesis of Z-vancosamine " starting from vinyl iodide and protected aldehyde via an intramolecular Kishi-Nozaki coupling reaction. The coupling product, as a mixture of alcohols, was immediately oxidized with DMP (Dess-Martin periodinane). The oxidation was followed by a sodium borohydride/cerium chloride reduction to produce a protected alcohol intermediate. In the next step, the required alcohol was reacted... 

The chain-growth catalyst is prepared by dissolving two moles of nickel chloride per mole of bidentate ligand (BDL) (diphenylphosphinobenzoic acid in 1,4-butanediol). The mixture is pressurized with ethylene to 8.8 MPa (87 atm) at 40°C. Boron hydride, probably in the form of sodium borohydride, is added at a molar ratio of two borohydrides per one atom of nickel. The nickel concentration is 0.001—0.005%. The 1,4-butanediol is used to solvent-extract the nickel catalyst after the reaction. 

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... 

A solution of 0.25 g sodium borohydride in 140 ml of ethanol is added to a stirred solution of 0.56 g of calcium chloride in 60 ml of ethanol at —25°. The vigorously stirred mixture is treated dropwise at —25° over 5 min with 4.87 g of 1 la-hydroxy-5/S-pregnane-3,20-dione in 100 ml of ethanol. After a further 3 hr at —20°, 10 ml of 40% aqueous acetic acid is added and the mixture is evaporated to dryness under vacuum. The residue is dissolved in 150 ml of ether and the ethereal solution is washed with 30 ml of 2 A hydrochloric acid and twice with 30 ml of water and dried over Na2S04. Removal of the solvent gives 4.6 g of crystals, which are recrystallized from 20 ml of ether to yield 2.9 g (60%) of the dihydroxy ketone, mp 182-184° [aj 110° (ethanol). 

Aniline 77 was converted into its diazonium salt with nitrous acid and this was followed by reduction with stannous chloride to afford the corresponding arylhydrazine 78. Condensation of 78 with 3-cyanopropanal dimethylacetal 79 gave the arylhydrazone 80. Treatment of 80 with PPE resulted in cyclization to indole 81. The nitrile group was then reduced to the primary amine by catalytic hydrogenation. Reaction of the amine with excess formalin and sodium borohydride resulted in Imitrex (82). 

Conjugate addition of methyl magnesium iodide in the presence of cuprous chloride to the enone (91) leads to the la-methyl product mesterolone (92) Although this is the thermodynamically unfavored axially disposed product, no possibility for isomerization exists in this case, since the ketone is once removed from this center. In an interesting synthesis of an oxa steroid, the enone (91) is first oxidized with lead tetraacetate the carbon at the 2 position is lost, affording the acid aldehyde. Reduction of this intermediate, also shown in the lactol form, with sodium borohydride affords the steroid lactone oxandrolone... 

The key intermediate 21 is in principle accessible in any of several ways. Thus reaction of thiophenecarbox-aldehyde with amninoacetal would lead to the Schiff base 20 treatment with acid would result in formation of the fused thiophene-pyridine ring (21). Alkylation of that intermediate with benzyl chloride gives the corresponding ternary imini urn salt 23. Treatment with sodium borohydride leads to reduction of the quinolinium ring and thus formation of ticlopidine (24). ... 

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]. 

D) Preparation of 2-(1-Hydroxyethyi)-3-Methyi-5-(2-Oxo-2,5-Dihydro-4-Furyi)Benzo[b] Furan (3574 CB) 13,2 grams of compound 3556 CB of which the preparation is described in (C) are treated successively with 66 ml of methylene chloride, 27 ml of methanol and, with stirring, 1.6 grams of sodium borohydride added in stages. The reaciton takes 1 hour. The mixture is poured into water acidified with a sufficient amount of acetic acid, the solvents are stripped under vacuum, the crystalline product removed, washed with water, and recrystallized from ethyl acetate. Yield 90%. MP <=158°C. 

A solution of N-(2-aminobenzvl)-1-phenyl-2-metKylaminoethanol-1 was prepared by the reaction of a-bromo-acetophenone and (2-nitrobenzyl)methylamine, followed by hydrogenation of the nitro group by means of nickei on diatomaceous earth at room temperature and reduction of the CO group by means of sodium borohydride. The intermediate thus produced was dissolved in 100 ml of methylene chloride and introduced dropwise into 125 ml of sulfuric acid at 10° to 15°C. After a short standing, the reaction mixture was poured onto ice and rendered alkaline by means of a sodium hydroxide solution. Dy extraction with ether, there was obtained 1,2,3,4-tetrahydro-2-methyl-4-phenyl-8-amino-iso-quinoline. The base is reacted with maleic acid to give the maleate melting point of the maleate 199° to 201°C (from ethanol). 

After evaporation of the solvent, the solid residue consists of 5-(2-chlorobenzyl)-thieno[3,2-cl -pyridinium chloride which melts at 166°C (derivative n°30). This compound is taken up into a solution comprising ethanol (300 ml) and water (100 ml). Sodium borohydride (NaBH4) (20 g) is added portionwise to the solution maintained at room temperature. The reaction medium is maintained under constant stirring during 1 2 hours and is then evaporated. The residue is taken up into water and made acidic with concentrated hydrochloric acid to destroy the excess reducing agent. The mixture is then made alkaline with ammonia and extracted with ether. The ether solution is washed with water, dried and evaporated. The oily residue is dissolved in isopropanol (50 ml) and hydrochloric acid in ethanol solution is then added thereto. 

Step D Chemical Reduction Preparation of 3-Morpholino-4-(3-tert-Butylamino-2-Hydroxy-propoxyl-l,2,5-Thiadiazole — The 3-morpholino-4-(3-tert-butylamino-2-oxopropoxy)-1,2,5-thiadiazole (0.01 mol) is dissolved in isopropanol (10 ml). To the solution is added sodium borohydride in portions until the initial evolution of heat and gas subsides. The excess sodium borohydride is destroyed by addition of concentrated hydrochloric acid until the mixture remains acidic. The precipitate of sodium chloride is removed, ether is added, and the solution is concentrated to crystallization. The solid material is removed by filtration and dried thus providing 3-morpholino-4-(3-tert-butylamino-2-hydroxypropoxy)-1,2,5-thiadiazole, MP 161° to 163°C (as hydrochloride). 

Intermediate 10 must now be molded into a form suitable for coupling with the anion derived from dithiane 9. To this end, a che-moselective reduction of the benzyl ester grouping in 10 with excess sodium borohydride in methanol takes place smoothly and provides primary alcohol 14. Treatment of 14 with methanesulfonyl chloride and triethylamine affords a primary mesylate which is subsequently converted into iodide 15 with sodium iodide in acetone. Exposure of 15 to tert-butyldimethylsilyl chloride and triethylamine accomplishes protection of the /Mactam nitrogen and leads to the formation of 8. Starting from L-aspartic acid (12), the overall yield of 8 is approximately 50%, and it is noteworthy that this reaction sequence can be performed on a molar scale. 

Preparation of the acetate derivative Concentrate the aqueous mixture of saccharides to approximately 0.5 ml in a 20-50 ml container. Reduce the saccharides by adding 20 mg of sodium borohydride that has been dissolved carefully into 0.5 ml of water and let the reducing mixture stand at room temperature for at least 1 hour. Destroy the excess sodium borohydride by adding acetic acid until the gas evolution stops. Evaporate the solution to dryness with clean nitrogen. Add 10 ml of methanol and evaporate the solution to dryness. Acetylate with 0.5 ml (three parts acetic anhydride and two parts pyridine) overnight. Evaporate to a syrupy residue and add 1 ml of water. Evaporate again to dryness to remove the excess acetic anhydride. Dissolve the residue in 250 /d methylene chloride. 

Epiberberine and berberine were stereoselectively converted to fumaritrine (421) and its analog via 8,14-cycloberbines 216). The cycloberbine 432, derived from epiberberine (431) in the established way, was treated with p-toluenesulfonic acid in methanol and then with methyl iodide to give stereoselectively the cis-fused indenobenzazepine 433 in excellent yield (Scheme 86). Deoxygenation of the hydroxyl group in 433 was accomplished by treatment with methanesulfonyl chloride and subsequent reduction with sodium borohydride in dimethoxyethane to give (+ )-fumaritrine (421) (216). 

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