Ethyl tetrahydrofuran-2-carboxylates

Ethyl tetrahydrofuran-2-carboxylates. p-Alkoxy carbonyl compounds in which the alkoxy group is readily detached in the presence of a Lewis acid undergo condensation with ethyl diazoacetate. Tin(IV) chloride is a suitable catalyst for P-alkoxy aldehydes, but it requires zirconium(IV) chloride to effect a reaction with P-alkoxy ketones. 

To a solution of 0.02M ethyl- 0 -ketocaprylate (or homolog) in 20 ml tetrahydrofuran, add 1.02g (0.02M) (53% oil) NaH with stirring and cooling and then add a solution of diketene (1.68g, 0.02M) in 20 ml tetrahydrofuran dropwise, keeping the temperature between -5 and 0° C. Stir 1 hour at this temperature and then 1 hour at room temperature. Neutralize with 10% HC1 and extract with ether. Dry and evaporate in vacuum to get about 38% yield of ethyl-olivetol carboxylate (I). (I) can be purified on silica gel, the impurities being eluted with petroleum ether (30-35° C) and the produce with 8 1 petroleum ethenether. Recrystallize from n-hexane. Dissolve 0.2g (I) in 10 ml 10% NaOH and reflux 30 minutes. Acidify with 10% HCI and extract with ether. Wash the extract with water and dry, evaporate in vacuum (can distill 126-129/3) to get 96% olivetol (or... 

Preparation of 7-amino-3-chloro-3-cephem-4-carboxylic acid To a solution of 750 mg (1 55 mmol) of p-nitrobenzyl 7-amino-3-chloro-3-cephem-4-carboxylate hydrochloride in 20 ml of tetrahydrofuran and 40 ml of methanol was added a suspension of 750 mg of prereduced 5% palladium on carbon catalyst in 20 ml of ethanol and the suspension was hydrogenated under 50 psi of hydrogen at room temperature for 45 minutes. The catalyst was filtered and washed with THF and water. The filtrate and catalyst washes were combined and evaporated to dryness. The residue was dissolved in a water-ethyl acetate mixture and the pH adjusted to pH 3. The insoluble product was filtered and triturated with acetone. The product was then dried to yield 115 mg of 7-amlno-3-chloro-3-cephem-4-carboxylic acid. 

An extension of these ring expansions involves the photolysis of bis(2-azidobenzoyl)ethyl-ene glycol (88) in methanol/tetrahydrofuran whereupon 1,2-ethanediyl bis(2-methoxy-3//-azepine-3-carboxylate) (89) is formed.198... 

C 7H,203 5675-70-7) see Bisantrene (R)-(-i)-tetrahydrofuran-2-carboxylic acid (CjHgOj 87392-05-0) see Faropenem sodium ( )-tetrahydrofuran-2-carboxylic acid (CjHgOg 16874-33-2) see Alfuzosin Faropenem sodium tetrahydro-2-furancarboxylic acid anhydride with ethyl hydrogen carbonate (CgHijO, 167391-50-6) see Alfuzosin... 

Hydrindene, see Indan Hydrindonaphthene, see Indan 1,8-Hydroacenaphthylene, see Acenaphthene Hydrobroinic ether, see Ethyl bromide Hydrocarbon propellant A-17, see Bntane Hydrochloric ether, see Chloroethane Hydrofuran, see Tetrahydrofuran Hydrogen carboxylic acid, see Formic acid Hydrophenol, see Cyclohexanol Hydroqninol, see Hydroquinone Hydroqninole, see Hydroquinone a-Hydroqninone, see Hydroquinone p-Hydroqninone, see Hydroquinone 6-Hydroxyacenaphthenone, see Acenaphthene Hydroxybenzene, see Phenol... 

A solution of borane in tetrahydrofuran reduces esters at room temperature only slowly [977]. Under such conditions free carboxylic groups of acids are reduced preferentially monoethyl ester of adipic acid treated with 1 mol of borane in tetrahydrofuran at — 18° to 25° gave 88% yield of ethyl 6-hydroxy-hexanoate [977]. Borane-dimethyl sulfide in tetrahydrofuran was used for... 

The reason why the carbonyl group in -santonin remained intact may be that, after the reduction of the less hindered double bond, the ketone was enolized by lithium amide and was thus protected from further reduction. Indeed, treatment of ethyl l-methyl-2-cyclopentanone-l-carboxylate with lithium diisopropylamide in tetrahydrofuran at — 78° enolized the ketone and prevented its reduction with lithium aluminum hydride and with diisobutyl-alane (DIBAL ). Reduction by these two reagents in tetrahydrofuran at — 78° to —40° or —78° to —20°, respectively, afforded keto alcohols from several keto esters in 46-95% yields. Ketones whose enols are unstable failed to give keto alcohols [1092]. 

In dicarboxylic acids with one free and one esterified carboxyl group the free carboxyl only may be reduced with hydrides (alanes, boranes). The monoethyl ester or adipic acid was converted by an equimolar amount of borane in tetrahydrofuran at —18° to 25° to ethyl 6-hydroxyhexanoate in 88% yield [971] Procedure 19, p. 209). 

The amidic group in methyl A -acetyl-p-aminobenzoate was reduced preferentially to an ester group with borane in tetrahydrofuran (1.5-1.8 mol per mol of the amide), giving 66% yield of methyl p-A -ethylaminobenzoate. Similarly l-benzyl-3-methoxycarbonyl-5-pyrrolidone afforded methyl l-ben2yl-3-pyr-rolidinecarboxylate in 54% yield and l,2-diethyl-5-ethoxycarbonyl-3-pyra-zolidone gave ethyl l,2-diethylpyrazolidine-3-carboxylate in 60% yield. 

Alternatively the oxidation of 4 -(methylsulfonyl) acetophenone with S8 and morpholine produces the 2-(4-(methylsulfonyl)phenyl)acetic acid ethyl ester (xiv), which is condensed with 2-methylpyridine-3-carboxylic acid methyl ester by means of terf-butyl magnesium chloride in hot tetrahydrofurane to give the ketosulfone (ix). 

Hydrogenation of 4-oxo-4//-pyrimido[2,l-a]isoquinoline-3-nitrile in tetrahydrofuran in the presence of ammonia over Raney nickel under 60 psi for 5 h yielded 3-aminomethyl-4//-pyrimido[2,l-a]isoquinolin-4-one (86EUP166439). Reduction of ethyl 4-oxo-4//-pyrimido[2,l-a]isoquino-line-3-carboxylate with diisobutylaluminum hydride in methylene chloride... 

Ethyl 2-(2-quinolinyl)-5-oxo-2,5-dihydroisoxazole-4-carboxylates (346) with aqueous sodium azide in tetrahydrofuran gave mixtures of ethyl 3-hydroxy-l-oxo-l//-pyrimido[l,2-a]quinoline-2-carboxylates (347) and quinoline derivatives (348-350) (95AJC1861). When the base-catalyzed rearrangement of 346 was carried out in 2-2.5 M aqueous sodium hydroxide for 30 min, ethyl 3-hydroxy-l-oxo-l//-pyrimido[l,2-a]quinoline-2-carbox-ylates (347, R = R2 = H, R1 = H, Me and R = H, R1 = Me, Ph, R2 = OMe) were obtained in 65-99% yields (89AJC2161 92AJC1825). Treatment of 2-(2-quinolinyl)-4-phenylisoxazol-5(2//)-one (351) with butyllithium and then with methyl iodide afforded 3-hydroxy-2-phenyl-l//-pyrimido[l,2-a]quinolin-l-one (352) (94AJC1673). 

The ethyl ester of l-cyclopropyl-7-(2,6-dimethyl-4-pyridyl)-5,6,8-trifluoro-4-oxo-1,4-di-hydroquinoline-3-carboxylic acid26 and of the closely related (7>)-10-(2,6-dimethyl-4-pyridyl)-8,9-difluoro-3-methyl-7-oxo-2.3-dihydro-7//-pyrido[1,2,3-tfe]-l,4-bcnzoxazine-6-carboxylic acid 427 can be thiolated in tetrahydrofuran at low temperature, using the strong base sodium hydride. 

The rearrangement of ethyl 2-(5-carboxy-2-pyridyl)-5-oxo-2,5-dihydro-isoxazole-4-carboxylate 118 (R = COOH, R1 = H) by the action of 2.5 M aqueous sodium hydroxide at 40°C for 10 minutes and in tetrahydrofuran by the action of saturated aqueous sodium carbonate solution at ambient temperature for 5 hours yielded pyrido[l,2-a]pyrimidine derivative 119 (R = COOH, R1 = H). The proposed reaction mechanism is depicted in Scheme 9 (89AJC2161). 

A solution of 6-chloro-3,4-dihydro-4-methyl-3-oxo-2H-l,4-benzoxazine-8-carboxylic acid in tetrahydrofuran and dimethylformamide is cooled to below 0°C and triethylamine is added under stirring thereto. Further, ethyl chlorocarbonate is added and the mixture is stirred at room temperature. To the resultant mixture is added 3-amino-8-azabicyclo[3.2.1]octane and the mixture stirred. After completion of the reaction, aqueous sodium hydrogen carbonate and ethyl acetate are added. The organic layer is separated, washed with water and dried over magnesium sulfate. The solvent is distilled off to give 6-chloro-3,4-dihydro-4-methyl-N-(8-azabicyclo[3.2.1]oct-3-yl)-3-oxo-2H-l,4-benzoxazine-8-carboxamide. 

To a stirred suspension of 3 g of methyl 2-endo-hydroxy-l-exo-hydroxymethyl-3a, 8b-cis-2,3,3a,8b-tetra hydro-1 H-5-cyclopenta[ bjbenzofuran-carboxylate in 30 ml of anhydrous tetrahydrofuran was added 1.5 ml of a solution which is obtained by dissolving 10 ml of 1,1-diethoxyethane and 200 mg of p-toluenesulfonic acid monohydrate into 10 ml of tetrahydrofuran followed by drying over molecular sieves, and the mixture was stirred for 14 hours at 60°C and then cooled. To the reaction mixture was added 100 mg of sodium hydrogen carbonate, and the mixture was stirred for 10 min at room temperature. Then, water was added to the reaction mixture and the mixture was extracted three times with ethyl acetate. The combined organic layers were washed with water and aqueous saturated solution of sodium chloride, was dried, and was concentrated to give 3.5 g of the crude crystals. The crude crystals were recrystallized from benzene-hexane to yield 2 g of the title compound (m.p. 162-163°C). 

To a solution of 1 equivalent (eq.) of lH-tetrazole-1-acetic acid and 1 eq. of triethylamine in 20 ml of tetrahydrofuran cooled to -20°C was added 1 eq. of pivaloyl chloride. After thirty-minute stirring of the mixture 20 ml of a chloroform solution containing 1 eq. of and 1 eq. of triethylamine was poured into the solution cooled at -10°C during a period of 30 minutes. The resulting mixed solution was stirred for 30 minutes at the same temperature, for 1 hour in an ice-water mixture and for 3 hours at room temperature. Removal of a solvent from the reaction mixture afforded an oily residue, which was dissolved into 15 ml of 10% sodium bicarbonate aqueous solution. The resulting aqueous layer was adjusted to pH 1.0-2.0 with 10% hydrochloric acid, washed with ether and extracted with ethyl acetate. The extract was washed with water, dried over sodium sulfate and concentrated under reduced pressure leaving a residue which was triturated with ethyl acetate to obtain 3-acetoxymethyl-8-oxo-7-(2-tetrazol-l-acetylamino)-5-thia-l-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid. 

A suspension of 3,4-dihydroxy-5-methanesulfonyloxy-cyclohex-l-ene-l-carboxylic acid methyl ester (20.78 g, 78 mmol) in tetrahydrofuran (400 ml) at 0°C was treated with l,8-diazabicyclo[5.4.0]undec-7-ene (11.7 ml, 78 mmol) and was stirred at room temperature for 9 h at which time the reaction was complete. The reaction was evaporated and the crude residue was dissolved in CH2CI2 (200 ml) and was washed with saturated NaCI (300 ml). The aqueous phase was extracted with CH2CI2 (2 times 200 ml). The combined organic extracts were dried (MgS04), filtered, and evaporated. The crude product was purified on silica gel (ethyl acetate) to afford 5-hydroxy-7-oxa-bicyclo[4.1.0]hept-3-ene-3-carboxylic acid methyl ester (12 g, 90%) as a white solid. 

A solution of 0.8 g of diethyl N-[l-methyl-3-(2-nitro-3-chlorophenyl)-3-oxopropylidene]aminomalonate in 4 ml of absolute tetrahydrofuran was added dropwise with stirring to a solution prepared with 8 ml of absolute ethanol and 100 mg of metallic sodium. After the reaction mixture was refluxed for 4.5 hours, the solvents were distilled off under reduced pressure. The residue was added with an ice-water and the solution was extracted with ether. The extract was washed with water, dried over anhydrous magnesium sulfate, after which ether was distilled off. The residue was recrystallized from benzene to obtain ethyl 3-(2-nitro-3-chlorophenyl)-5-methylpyrrole-2-carboxylate as colorless needles having MP 220°-223°C. 

The ethyl 2-pentafluorobenzoyl-3-cyclopropylaminoacrylate (28 g) was dissolved in dry tetrahydrofuran and allowed to react with 60% sodium hydride (3.85 g) at room temperature to give ethyl l-cyclopropyl-5,6,7,8-tetrafluoro-l,4-dihydro-4-oxoquinoline-3-carboxylate (18.4 g), melting point 170°-171°C. 

Tetrahydrofuran (250 cm3), ethyl (la,5a,6a)-7-(6-benzylidenylamino-3-azabicyclo[3.1.0]hex-3-yl)-l-(2,4-difluorophenyl)-6-fluoro-l,4-dihydro-4-oxo-l,8-naphthyridine-3-carboxylate (25.05 g, 47 mmol) obtained above, and water (250 cm3) were treated with 97% methanesulfonic acid (13.3 g, 138 mmol) and heated to reflux for 24 h. The resulting solution was cooled to 45°C, treated with activated carbon (2.5 g) for 1 h and filtered. The resulting filtrate was concentrated under vacuum to approximately 25% of its original volume to provide a white crystal slurry, cooled to 15°-25°C, granulated for 4 h and filtered to yield the trovafloxacin methanesulfonate salt (mesylate) (16.86 g, 70.0%). Melting point 253°-256°C decomp. 

To a solution of 34.6 g of 2-(pyrrol-l-yl)benzyl alcohol in 300 ml of anhydrous tetrahydrofuran and 32 ml of tetramethylethylene diamine is added 183 ml of a 2.4 molar solution of n-butyl lithium in such a manner that the internal temperature of the reaction is maintained below 30°C. On completion of the addition, the reaction mixture is stirred at room temperature for 3 hours. The reaction mixture is then cooled to -70°C by means of a dry-ice/acetone bath, and 24 ml of ethyl pyruvate is added to the mixture over 1 minute. The reaction is then allowed to warm to room temperature and stirred overnight (18 hours). The reaction is then poured into an ice-water/ether mixture and the organic phase separated, dried over magnesium sulfate and the solvent evaporated under reduced pressure to yield ethyl-4-methyl-4H,6H-pyrrolo[l,2-a][4,l]benzoxazepine-4-carboxylate, MP 94°-96°C, which may be recrystallized from a mixture of ether-hexane (1 1). 

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