sodium;propan-2-olate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In the formula, R3a, R4a and X4 have the same meanings as defined above; R2b represents an optionally substituted alkyl group; and Y represents a lower alkyl group. The compound (xxxiii) according to the present invention can be produced from (xxvi) and (xix) through steps 10-(1) to 10-(7) (intermediates (xxvii) to (xxxii)). The compound (xxvii) can be produced by condensation of (xxvi) with (xix) (step 10-(1)). The base used varies depending on the starting material, the solvent used etc., and is not particularly limited so long as it is inert to the reaction. Preferably, potassium tert-butoxide etc. may be proposed. The solvent used varies depending on the starting material, reagents etc., and is not particularly limited insofar as it is inert to the reaction and dissolves the starting material to a certain degree. tert-Butanol is preferred. The reaction temperature is preferably room temperature to 120° C., more preferably around room temperature. The compound (xxxviii) can be produced by alkylating (xxvii) with methyl halide in the presence of a base (step 10-(2)). The base used in the reaction varies depending on the starting material, the solvent used etc., and is not particularly limited so long as it is inert to the reaction. Preferably, an inorganic base such as potassium carbonate etc. may be proposed. Preferable example of the methyl halide is methyl iodide. The solvent used varies depending on the starting material, reagents etc., and is not particularly limited insofar as it is inert to the reaction and dissolves the starting material to a certain degree. Preferably, a ketone such as acetone or methyl ethyl ketone may be proposed. The reaction temperature is preferably room temperature to 12° C, more preferably around room temperature. The 2-oxo-1,2-dihydro-3-pyridyl carbonitrile derivative (xxix) can be produced by reacting (xxviii) with 2-cyanoacetamide in the presence of a base (step 10-(3)). The base used varies depending on the starting material, the solvent used etc., and is not particularly limited so long as it is inert to the reaction. Preferably, an alkali metal alkoxide such as sodium methoxide, sodium ethoxide, sodium isopropoxide, potassium tert-butoxide etc. may be proposed. The solvent used varies depending on the starting material, reagents etc., and is not particularly limited insofar as it is inert to the reaction and dissolves the starting material to a certain degree. Preferably, N,N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, isopropanol etc. The reaction temperature is preferably 0° C. to 120° C. The compound (xxx) can be produced by alkylating an oxygen atom at the 2-position of (xxix) with 2-halogenoacetamide in the presence of a base (step 10-(4)) As the 2-halogenoacetamide used, 2-chloroacetamide is preferred, and the reaction in which sodium iodide is further added is more preferred. The base used varies depending on the starting material, the solvent used etc., and is not particularly limited so long as it is inert to the reaction. Preferably, sodium hydride, sodium hydroxide, potassium hydroxide, sodium bicarbonate, sodium carbonate and potassium carbonate may be proposed. The solvent used varies depending on the starting material, reagents etc., and is not particularly limited so long as it is inert to the reaction and dissolves the starting material to a certain degree. Preferably, ketones such as acetone or methyl ethyl ketone, alcohols such as methanol or ethanol, ethers such as tetrahydrofuran, dioxane, dimethoxyethane or diethylene glycol dimethyl ether, N,N-dimethylformamide, dimethyl sulfoxide, 1-methyl pyrrolidinone, etc. may be proposed. The reaction temperature is usually 0 to 100° C. The compound (xxxi) can be produced by transaminating the 2-aminocarbonylmethyloxy-3-cyanopyridine derivative (xxx) in the presence of a base in a solvent (step 10-(5)). The base used varies depending on the starting material, the solvent used etc., and is not particularly limited so long as it is inert to the reaction. Preferably, sodium hydride, sodium hydroxide, potassium hydroxide, sodium bicarbonate, sodium carbonate, potassium carbonate etc. may be proposed. The solvent used varies depending on the starting material, the solvent used etc., and is not particularly limited unless it is inert to the reaction. Preferably, ketones such as acetone or methyl ethyl ketone, alcohols such as methanol, ethanol, propanol or butanol, ethers such as tetrahydrofuran, dioxane, dimethoxyethane or diethylene glycol dimethyl ether, N,N-dimethylformamide, dimethyl sulfoxide, 1-methyl pyrrolidinone, etc. may be proposed. The reaction temperature is usually room temperature to 150° C. The compound (xxii) can be produced by halogenating the 5-position of the pyridine ring in the 2-aminonicotinonitrile derivative (xxxi) with a halogenating agent in a solvent (step 10-(6)). The halogenating agent used varies depending on the starting material, the solvent used etc., and is not particularly limited so long as it is inert to the reaction. Preferably, N-bromosuccinimide, bromine etc. may be proposed. The solvent used varies depending on the starting material, reagents etc., and is not particularly limited insofar as it is inert to the reaction and dissolves the starting material to a certain degree. Preferably, alcohols such as methanol or ethanol etc., ethers such as tetrahydrofuran, dioxane, dimethoxyethane or diethylene glycol dimethyl ether etc., N,N-dimethylformamide, 1-methyl pyrrolidinone etc. may be proposed. The reaction temperature is usually −20° C. to room temperature. The compound (xxxiii) according to the present invention can be produced by allowing the aryl tin reagent obtained in Production Process 5 to act on the 2-amino-5-halogenonicotinonitrile derivative (xxxii) in the presence of a palladium catalyst in a solvent, to introduce an aromatic group into the 5-position of the pyridine ring in (xxxii) (step 10-(7)). As the palladium catalyst used is, for example, dichlorobis(triphenylphoshine) palladium (II), palladium (II) acetate, tetrakis(triphenylphosphine) palladium (0), tris(dibenzylidene acetone) dipalladium (0), dichlorobis(acetonitrile) palladium (II) etc. are preferred. The solvent used varies depending on the starting material, reagents etc., and is not particularly limited insofar as it is inert to the reaction and dissolves the starting material to a certain degree. Preferably, alcohols such as methanol or ethanol, ethers such as tetrahydrofuran, dioxane, dimethoxyethane or diethylene glycol dimethyl ether, toluene, xylene, N,N-dimethylformamide, 1-methyl pyrrolidinone etc. may be proposed. The reaction temperature is usually room temperature to 150° C. is inert to the reaction is inert to the reaction dissolves the starting material to a certain degree is preferably 0° C. to 120° C

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 116.5 g of the sodium salt of chloracetic acid are slowly added at 80° C. to a sodium isopropoxide solution (freshly prepared from 23 g of sodium and 250 ml of isopropylalcohol). The reaction mixture is refluxed for 2 hours and then combined with 500 ml of water. The mixture is evaporated down to a total volume of 200 ml and adjusted to pH1 with conc. sulphuric acid. The precipitate formed is filtered off, the two phases of the filtrate are and the organic phase is fractionally distilled in vacuo (101–103° C./10 Torr; 83 g; 70%). The 2-isopropoxy-acetic acid thus obtained is heated together with 0.2 ml of conc. sulphuric acid in 57 ml of methanol and 200 ml benzene for 7 hours using a water separator. After the excess methanol has been distilled off the residue is fractionally distilled in vacuo (50–55° C./10 Torr; 81.6 g; 88%). The reaction mixture is refluxed for 2 hours The mixture is evaporated down to a total volume of 200 ml The precipitate formed is filtered off the organic phase is fractionally distilled in vacuo (101–103° C./10 Torr; 83 g; 70%)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 5.19 g of diethyl 1-benzyl-2-bromomethylimidazole-4,5-dicarboxylate [prepared as described in Preparation 42(ii)] in 20 ml of isopropanol and 25 ml of tetrahydrofuran was added dropwise to a solution of sodium isopropoxide in isopropanol (prepared from 0.77 g of sodium and 100 ml of isopropanol), and then, the resulting mixture was heated under reflux for 5 hours. The reaction solution was then treated following a procedure similar to that described in Preparation 42 (iii). The residue was purified by column chromatography through silica gel, using a 3:2 by volume mixture of hexane and ethyl acetate as the eluent, to give 1.47 g of the title compound as a syrup. the resulting mixture was heated under reflux for 5 hours The reaction solution was then treated The residue was purified by column chromatography through silica gel by volume mixture of hexane and ethyl acetate as the eluent

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 5.19 g of diethyl 1-benzyl-2-bromomethylimidazole-4,5-dicarboxylate [prepared as described in Preparation 42(ii)] in 20 ml of isopropanol and 25 ml of tetrahydrofuran was added dropwise to a solution of sodium isopropoxide in isopropanol (prepared from 0.77 g of sodium and 100 ml of isopropanol), and then, the resulting mixture was heated under reflux for 5 hours. The reaction solution was then treated following a procedure similar to that described in Preparation 42 (iii). The residue was purified by column chromatography through silica gel, using a 3:2 by volume mixture of hexane and ethyl acetate as the eluent, to give 1.47 g of the title compound as a syrup. the resulting mixture was heated under reflux for 5 hours The reaction solution was then treated The residue was purified by column chromatography through silica gel by volume mixture of hexane and ethyl acetate as the eluent

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of methyl 2-[N-(2-dimethylaminoethyl)aminosulfonyl]-6-nitrobenzoate hydrochloride (12.0 g, 32.6 mmol) in dry isopropanol (500 mL) containing sodium isopropoxide (39 mmol) was stirred at reflux under N2 for 18 hours. After adding glacial acetic acid (1 mL) and concentrating under reduced pressure, the residue was partitioned between ethyl acetate and water. The ethyl acetate extract was washed with a saturated aqueous solution of sodium chloride, dried (Na2SO4), filtered and concentrated. The residue was converted to the hydrochloride salt with ethanolic anhydrous hydrogen chloride and recrystallized from methanol - ethyl acetate to give 4.0 g (31%) of product, m.p. 187.0-190.0° dec. Anal Calc'd for C14H21N3O6S.HCl: C, 42.47; H, 5.60; N, 10.61 at reflux under N2 for 18 hours concentrating under reduced pressure the residue was partitioned between ethyl acetate and water The ethyl acetate extract was washed with a saturated aqueous solution of sodium chloride dried (Na2SO4) filtered concentrated recrystallized from methanol - ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Similarly, when Example 4(a) is repeated except that DMSO is replaced by a volumetrically equivalent amount of DMF or DMAC and sodium methoxide is replaced by a stoichiometrically equivalent amount of sodium ethoxide, sodium n-propoxide, sodium isopropoxide, or sodium tert-butoxide respectively, a mixture of picramide and DATB is produced. The DATB is purified by crystallization from DMF and DMSO.

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of sodium isopropoxide in THF was prepared by the reaction of 45 g (1125 mmole) of 60% sodium hydride with 84 ml (1100 mmole) of isopropyl alcohol in 400 ml of THF. This solution was added, with mechanical stirring, to 83.4 g (490 mmole) of thiophosphorylchloride in 300 ml of THF and cooled to -40° C. internal. After the addition was complete the reaction mixture was slowly warmed to 25° C. When gas chromatography showed the reaction to be complete the THF was removed in vacuo and the product partitioned between hexanes and water. The organic layer was dried over anhydrous magnesium sulfate and concentrated in vacuo yielding 93 g of the title compound, an oil. nmr 1.4 d 12H, 4.9 m 2H. After the addition was slowly warmed to 25° C the reaction was removed in vacuo the product partitioned between hexanes and water The organic layer was dried over anhydrous magnesium sulfate concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6.9 grams (0.300 mole) of sodium were completely dissolved in a mixture of 200 ml of anhydrous isopropanol and 100 ml of tetrahydrofuran. 25.0 grams (0.0948 mole) of anhydrous (H2O content<100 ppm) of gadolinium trichloride was added in portions to the sodium isopropoxide solution. The resulting mixture was stirred at reflux for 5 hours. After 24 hours of sedimentation at room temperature, a transparent, colorless solution of gadolinium triisopropoxide in the alcohol-THF solution resulted. About 100 ml of the resultant solution were evacuated in Schlenk vessel and the dried residue was subsequently dissolved in 150 ml of deoxygenated, anhydrous, dimethylformamide. The remaining solution was analyzed for Gd(3) content by EDTA titration in the presence of urotropin buffer with xylenol orange as the metallochromic indicator. at reflux for 5 hours

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6.9 grams (0.300 mole) of sodium were completely dissolved in a mixture of 200 ml of anhydrous isopropanol and 100 ml of tetrahydrofuran. 25.0 grams (0.0948 mole) of anhydrous (H2O content<100 ppm) of gadolinium trichloride was added in portions to the sodium isopropoxide solution. The resulting mixture was stirred at reflux for 5 hours. After 24 hours of sedimentation at room temperature, a transparent, colorless solution of gadolinium triisopropoxide in the alcohol-THF solution resulted. About 100 ml of the resultant solution were evacuated in Schlenk vessel and the dried residue was subsequently dissolved in 150 ml of deoxygenated, anhydrous, dimethylformamide. The remaining solution was analyzed for Gd(3) content by EDTA titration in the presence of urotropin buffer with xylenol orange as the metallochromic indicator. at reflux for 5 hours

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 12 L 3-necked round-bottomed flask fitted with a mechanical stirrer, a thermometer, an addition funnel and a reflux condenser with a nitrogen inlet are charged 3-chloro-5-methoxybenzo[b]thiophene-2-carbonyl chloride (Example 1) (336 g) and THF (2.3 L). The solution of sodium isopropoxide from above is charged to the THF solution of the acid chloride in four portions causing the temperature of the reaction mixture to rise to 60° C. The flask which contains the sodium isopropoxide is rinsed with THF (275 mL) and the rinse is added to the 12 L reaction flask. The mixture is heated under reflux for 7 hours and then cooled to room temperature and stirred for 12 hours. After cooling to 5° C. to 10° C., concentrated hydrochloric acid (85 mL) is added and the dark mixture stirred for 1 hour to give a final pH of 1.5. The reaction is filtered through filter paper and the filter cake is washed with THF (200 mL). The clear filtrates are charged to a 12 L 3-necked round-bottomed flask fitted with a mechanical stirrer, a thermometer, and a distillation head with reflux condenser and THF is distilled out of the flask under low vacuum to a batch temperature of 50° C. Heptane (3.1 L) is charged to the flask and the slurry is cooled to 5° C. and filtered through filter paper. The filter cake is washed with heptane (300 mL) and the combined filtrates are washed with a sodium bicarbonate solution (3×390 mL) prepared by dissolving sodium bicarbonate (47 g) in deionized water (1170 mL). The heptane solution is charged to a 12 L 3-necked round-bottomed flask fitted with a mechanical stirrer, a thermometer, and a distillation head with reflux condenser and heptane is distilled out of the flask under low vacuum to a batch temperature of 70° C. Upon cooling, IPA (815 mL) and a solution of potassium hydroxide (392 g) in deionized water (1570 mL) are charged to the 12 L flask. The distillation head is replaced with a reflux condenser and the dark solution is heated to reflux and stirred for 4 hours and then cooled to room temperature and stirred for 16 hours. The reflux condenser is again replaced with a distillation head and IPA is distilled out at atmospheric pressure to a batch temperature of 95° C. Deionized water (1570 mL) is added to the solution which is then cooled to 5° C. to 10° C. and adjusted to pH 8 using concentrated hydrochloric acid (480 mL). The aqueous solution is extracted with methyl isobutyl ketone (MIBK) (2×500 mL) and the combined MIBK extracts are extracted with deionized water (300 mL). The aqueous solutions are combined and stirred with PWA carbon (50 g) at room temperature for 16 hours. The solution is filtered through filter paper coated with supercel and the filter cake is washed with deionized water (2×300 mL). The pale yellow filtrates are transferred to a 12 L 3-necked round-bottomed flask fitted with a mechanical stirrer and a thermometer. With agitation, the solution is cooled to 5° C. to 10° C. and concentrated hydrochloric acid (70 mL) is added to give a final pH of 2. The slurry is stirred for 2 hours at 5° C. to 10° C. and the crude product is collected on filter paper and washed with deionized water (3×400 mL). The off-white product is dried in a vacuum oven at 50° C. to afford 215.1 g of the title compound; To a 12 L 3-necked round-bottomed flask fitted with a mechanical stirrer to rise to 60° C is rinsed with THF (275 mL) the rinse is added to the 12 L reaction flask The mixture is heated under reflux for 7 hours After cooling to 5° C. to 10° C. concentrated hydrochloric acid (85 mL) is added the dark mixture stirred for 1 hour to give a final pH of 1.5 The reaction is filtered through filter paper the filter cake is washed with THF (200 mL) The clear filtrates are charged to a 12 L 3-necked round-bottomed flask fitted with a mechanical stirrer a thermometer, and a distillation head with reflux condenser THF is distilled out of the flask under low vacuum to a batch temperature of 50° C Heptane (3.1 L) is charged to the flask the slurry is cooled to 5° C. filtered through filter paper The filter cake is washed with heptane (300 mL) the combined filtrates are washed with a sodium bicarbonate solution (3×390 mL) prepared fitted with a mechanical stirrer a thermometer, and a distillation head with reflux condenser heptane is distilled out of the flask under low vacuum to a batch temperature of 70° C Upon cooling IPA (815 mL) and a solution of potassium hydroxide (392 g) in deionized water (1570 mL) are charged to the 12 L flask The distillation head is replaced with a reflux condenser the dark solution is heated to reflux stirred for 4 hours cooled to room temperature stirred for 16 hours is distilled out at atmospheric pressure to a batch temperature of 95° C Deionized water (1570 mL) is added to the solution which is then cooled to 5° C. to 10° C. The aqueous solution is extracted with methyl isobutyl ketone (MIBK) (2×500 mL) the combined MIBK extracts are extracted with deionized water (300 mL) stirred with PWA carbon (50 g) at room temperature for 16 hours The solution is filtered through filter paper the filter cake is washed with deionized water (2×300 mL) The pale yellow filtrates are transferred to a 12 L 3-necked round-bottomed flask fitted with a mechanical stirrer With agitation, the solution is cooled to 5° C. to 10° C. concentrated hydrochloric acid (70 mL) is added to give a final pH of 2 The slurry is stirred for 2 hours at 5° C. to 10° C. the crude product is collected on filter paper washed with deionized water (3×400 mL) The off-white product is dried in a vacuum oven at 50° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 12 L 3-necked round-bottomed flask fitted with a mechanical stirrer, a thermometer, an addition funnel and a reflux condenser with a nitrogen inlet are charged 3-chloro-5-methoxybenzo[b]thiophene-2-carbonyl chloride (Example 1) (336 g) and THF (2.3 L). The solution of sodium isopropoxide from above is charged to the THF solution of the acid chloride in four portions causing the temperature of the reaction mixture to rise to 60° C. The flask which contains the sodium isopropoxide is rinsed with THF (275 mL) and the rinse is added to the 12 L reaction flask. The mixture is heated under reflux for 7 hours and then cooled to room temperature and stirred for 12 hours. After cooling to 5° C. to 10° C., concentrated hydrochloric acid (85 mL) is added and the dark mixture stirred for 1 hour to give a final pH of 1.5. The reaction is filtered through filter paper and the filter cake is washed with THF (200 mL). The clear filtrates are charged to a 12 L 3-necked round-bottomed flask fitted with a mechanical stirrer, a thermometer, and a distillation head with reflux condenser and THF is distilled out of the flask under low vacuum to a batch temperature of 50° C. Heptane (3.1 L) is charged to the flask and the slurry is cooled to 5° C. and filtered through filter paper. The filter cake is washed with heptane (300 mL) and the combined filtrates are washed with a sodium bicarbonate solution (3×390 mL) prepared by dissolving sodium bicarbonate (47 g) in deionized water (1170 mL). The heptane solution is charged to a 12 L 3-necked round-bottomed flask fitted with a mechanical stirrer, a thermometer, and a distillation head with reflux condenser and heptane is distilled out of the flask under low vacuum to a batch temperature of 70° C. Upon cooling, IPA (815 mL) and a solution of potassium hydroxide (392 g) in deionized water (1570 mL) are charged to the 12 L flask. The distillation head is replaced with a reflux condenser and the dark solution is heated to reflux and stirred for 4 hours and then cooled to room temperature and stirred for 16 hours. The reflux condenser is again replaced with a distillation head and IPA is distilled out at atmospheric pressure to a batch temperature of 95° C. Deionized water (1570 mL) is added to the solution which is then cooled to 5° C. to 10° C. and adjusted to pH 8 using concentrated hydrochloric acid (480 mL). The aqueous solution is extracted with methyl isobutyl ketone (MIBK) (2×500 mL) and the combined MIBK extracts are extracted with deionized water (300 mL). The aqueous solutions are combined and stirred with PWA carbon (50 g) at room temperature for 16 hours. The solution is filtered through filter paper coated with supercel and the filter cake is washed with deionized water (2×300 mL). The pale yellow filtrates are transferred to a 12 L 3-necked round-bottomed flask fitted with a mechanical stirrer and a thermometer. With agitation, the solution is cooled to 5° C. to 10° C. and concentrated hydrochloric acid (70 mL) is added to give a final pH of 2. The slurry is stirred for 2 hours at 5° C. to 10° C. and the crude product is collected on filter paper and washed with deionized water (3×400 mL). The off-white product is dried in a vacuum oven at 50° C. to afford 215.1 g of the title compound; To a 12 L 3-necked round-bottomed flask fitted with a mechanical stirrer to rise to 60° C is rinsed with THF (275 mL) the rinse is added to the 12 L reaction flask The mixture is heated under reflux for 7 hours After cooling to 5° C. to 10° C. concentrated hydrochloric acid (85 mL) is added the dark mixture stirred for 1 hour to give a final pH of 1.5 The reaction is filtered through filter paper the filter cake is washed with THF (200 mL) The clear filtrates are charged to a 12 L 3-necked round-bottomed flask fitted with a mechanical stirrer a thermometer, and a distillation head with reflux condenser THF is distilled out of the flask under low vacuum to a batch temperature of 50° C Heptane (3.1 L) is charged to the flask the slurry is cooled to 5° C. filtered through filter paper The filter cake is washed with heptane (300 mL) the combined filtrates are washed with a sodium bicarbonate solution (3×390 mL) prepared fitted with a mechanical stirrer a thermometer, and a distillation head with reflux condenser heptane is distilled out of the flask under low vacuum to a batch temperature of 70° C Upon cooling IPA (815 mL) and a solution of potassium hydroxide (392 g) in deionized water (1570 mL) are charged to the 12 L flask The distillation head is replaced with a reflux condenser the dark solution is heated to reflux stirred for 4 hours cooled to room temperature stirred for 16 hours is distilled out at atmospheric pressure to a batch temperature of 95° C Deionized water (1570 mL) is added to the solution which is then cooled to 5° C. to 10° C. The aqueous solution is extracted with methyl isobutyl ketone (MIBK) (2×500 mL) the combined MIBK extracts are extracted with deionized water (300 mL) stirred with PWA carbon (50 g) at room temperature for 16 hours The solution is filtered through filter paper the filter cake is washed with deionized water (2×300 mL) The pale yellow filtrates are transferred to a 12 L 3-necked round-bottomed flask fitted with a mechanical stirrer With agitation, the solution is cooled to 5° C. to 10° C. concentrated hydrochloric acid (70 mL) is added to give a final pH of 2 The slurry is stirred for 2 hours at 5° C. to 10° C. the crude product is collected on filter paper washed with deionized water (3×400 mL) The off-white product is dried in a vacuum oven at 50° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 10 g. of 7-methoxy-3,7-dimethyloctan-1-al, 17 g. of diethyl 3-ethoxycarbonyl-2-methylprop-2-enyl phosphonate (77% trans), and 150 ml. of dimethylformamide, under nitrogen, 0°, with stirring, is added sodium isopropanolate (prepared from 1.5 g. of sodium in 150 ml. of isopropanol). After addition is complete, the reaction is stirred for 18 hours at room temperature and then worked up by extraction with hexane to yield isopropyl 11-methoxy-3,7,11-trimethyldodeca-2,4-dienoate (mostly trans-2,trans-4), which can be chromatographed and distilled for further purification. To a mixture of 10 g After addition worked up by extraction with hexane