KR950011103B1 - Preparation of 6,10,14,18-tetrasmethyl-5,9,13,17-nonadecatetraene-2-one - Google Patents

Abstract

6,10,14,18-Tetramethyl-5,9,13,17-nonadekatetraen-2-on of formula (I) is prepared by : reacting the cpd. of formula (4) with the cpd. of formula (7) to obtain the cpd. of formula (8); treating the cpd. (8) to obtain the cpd. of formula (9); and removing the protecting gp. from the cpd. (9). In the formulas, R is lower alkyl, bezene or toluene; m is 0 or 1; n is 1 or 2 (if m=0 then n=2, if m=1 then n=1); X is halogen. The obtd. cpd. (I) is useful for treatment of ulcer.

Description

Method for preparing 6,10,14,18-tetramethyl-5,9,13,17-nonadecatetraen-2-one

The present invention relates to a method for preparing 6,10,14,18-tetramethyl-5,9,13,17-nonadecatetraen-2-one of formula (I).

The compound of formula (I) is a known compound and is known as a compound having an antiulcer effect. The compound of formula (I) is described in EP 207 505.

The compound of formula (I) is prepared by condensation reaction of a compound of formula (III) with a compound of formula (IV), followed by decarboxylation,

Alternatively, the compound of formula (V) is prepared by reacting with the compound of formula (IV).

However, the above production method has a problem in that the production method of the starting material is complicated and the yield is also low.

The present inventors have conducted a long study on the preparation method of the compound of the formula (I), and as a result, by developing a method for producing a compound of the formula (I) which is an oral compound with a high yield and purity by a simple method Completed.

It is therefore an object of the present invention to provide an improved process for the preparation of compounds of formula (I).

The invention is explained in detail in the following.

The present invention is obtained by reacting a compound of the general formula (4) with a compound of the following general formula (7) and then removing a protecting group from the compound of the following general formula (9) To prepare a compound of formula (I).

Wherein R is lower alkyl, benzene, toloene, m is 0 or 1, n is 1 or 2 (where n is 2 if m is 0 and n is 1 at the same time) It is an atom.

The compound of formula (4) is prepared by reacting a compound of formula (1) with ethylene glycol to protect a carbonyl group to prepare a compound of formula (2), and then introducing a hydroxyl group to the formula (3). ) Is prepared by converting the hydroxyl group to a halogen group, represented by the reaction scheme.

Wherein m and x are as described above.

The compound of the general formula (7) is prepared by converting the hydroxyl group of the compound of the general formula (5) to a halogen function and then replacing with an alkyl or arylsulfonyl group.

Wherein R, n and X are as described above.

The compound of the general formula (1) and the compound of the general formula (5) are known compounds.

Synthesis of the compound of the general formula (2) in the general formula (1) is carried out by the catalytic amount of paratoluenesulfonic acid in the aromatic hydrocarbon such as benzene, toluene and the like or in a conventional solvent which is not involved in other reactions. It is prepared by reacting with ethylene glycol in the presence of a catalytic amount of sulfonic acid such as benzene sulfonic acid and the like.

Synthesis of the compound of the general formula (3) is carried out in combination with t-butyl hydroperoxide in the presence of a catalytic amount of an oxide such as selenium dioxide in a chlorinated hydrocarbon solvent such as methylene chloride or other common inert solvents. Prepared by oxidation with the same organic peroxide.

Synthesis of the compound of general formula (4) is prepared by halogenating the compound of general formula (3) with conventional halogenating agents in DMF, methylene chloride and other common inert organic solvents under conventional reaction conditions.

Preparation of compound represented by the general formula (6) from a compound represented by the general formula (5) PBr _3, PCl _3, and from conventional inert solvents which do not take part in an aliphatic hydrocarbon or aromatic hydrocarbon or or other reaction such as benzene, toluene, hexane Prepared by halogenation with a conventional halogenating agent.

Preparation of the compound of the general formula (7) may be carried out by combining the compound of the general formula (6) with an alkali metal salt of sulfinic acid, such as It is made by reaction.

This is expressed as a reaction scheme as follows.

Wherein R, X and n are as described above.

According to the method of the present invention, no reaction by-products are generated, and thus the target compound can be prepared purely, and the target compound can be prepared in high yield.

The intermediate compounds produced in the present invention are all novel materials and these novel materials and preparation methods thereof are also included within the scope of the present invention.

Next, the present invention will be described in more detail with reference to Examples.

Example 1

Synthesis of 6, 10-dimethyl-5,9-undecanedien-2-one ethylene acetal

Experimental method: Dissolve 25 ml two-necked flask geranyl acetone (97 mg, 5 mmol) in anhydrous benzene (10 ml), add ethylene glycol (435 mg, 7 mmol) and p-TsOH (3 mg), and then install a Dean-Stark trap. A reflux condenser was installed thereon and refluxed for 9 hours. The reaction mixture was cooled to room temperature, saturated aqueous sodium bicarbonate solution was added to separate the benzene layer, and the aqueous layer was extracted three times with petroleum ether.

The combined organic layers were washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a crude product. This crude product was obtained by column chromatography on benzene to give an oil (1.11G, 93%).

¹ H NMR (CDCl ₃ ): δ 5.09 (m, 2H) 3.9 (s, 4H) 1.8-2.16 (m, 8H) 1.66 (s, 3H) 1.56 (s, 6H) 1.30 (s, 3H)

IR (Vmax, cm ^-1 ): 2970, 2870, 1440, 1380, 1220, 1135, 1055, 950, 865

Example 2

Synthesis of 11-hydroxy-6,10-dimethyl-5,9-undecanedien-2-one ethylene acetal

Experimental Method: Suspension of selenium dioxide (55, 48 mg, 0.5 mmol) in dichloromethane in a 25 ml flask was added with 70% t-butyl hydroperoxide (180.24 mg, 0.5 mmol) and blocked in light 30 While stirring for 6 minutes, 6,10-dimethyl-5,9-undecanedien-2-one ethylene acetal (238 mg, 1.0 mmol) was added dropwise at 0 ° C. The reaction mixture is kept at 10 ° C., stirred for 5 hours and diluted with dichloromethane. The pale yellow diluent was washed with water and dilute aqueous sodium hydroxide solution, washed with water and brine again, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give a yellow oil. The yellow oil was dissolved in 5 ml of methanol, cooled using an ice bath, sodium borohydride (22 mg) was added and stirred at room temperature for 40 minutes. The solvent was evaporated under reduced pressure, the same amount of ether and water was added to the filtrate and then extracted three times with ether. The combined organic layers were washed with water and brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography with ethyl acetate and hexane (1: 3) mixed solution to give a colorless oil (104 mg, 41%).

¹ H NMR (CDCl ₃ ): δ 4.96-5.56 (m, 2H) 3.98 (s, 2H) 3.96 (s, 4H) 1.96-2.16 (m, 8H) 1.67 (s, 6H) 1.33 (s, 3H)

IR (Vmax, cm ^-1 ): 3400, 2870, 1380, 1270, 1060, 950, 860

Example 3

Synthesis of 11-chloro-6,10-dimethyl-5,9-undecanedien-2-one ethylene acetal

Experimental Method: Put allyl alcohol (254 mg, 1 mmol) and 2,4,6-collidine (133 mg, 1.1 mmol) in a 10 ml flask, stir through a stream of nitrogen, and dissolve in a small amount of anhydrous DMF. (42 mg, 1 mmol) was added and cooled to 0 ° C. Methanesulfonyl chloride (85 µl, 1.1 mmol) was added dropwise thereto and stirred at the same temperature for 1 hour 30 minutes. Cooled water was added to the reaction mixture, and the aqueous layer was extracted three times with pentane. The combined organic layers were washed several times with water and saturated aqueous copper nitrate solution, and subsequently washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give an oil (257 mg, 94%).

¹ H NMR (CDCl ₃ ): δ5.50 (m, 1H) 5.13 (m, 1H) 4.03 (s, 2H) 3.96 (s, 4H) 1.90-2.26 (m, 8H) 1.73 (s, 3H) 1.63 ( s, 3H) 1.33 (s, 3H)

IR (Vmax, cm ^-1 ): 2970, 2930, 2870, 1440, 1380, 1260, 1210, 1135, 1055, 940, 870, 685

Example 4

Synthesis of Geranyl Bromide

Experimental Method: Geraniol (400 mg, 2.59 mmol) was dissolved in 3 ml of anhydrous hexane in a 10 ml two-necked flask and cooled using an ice bath. Phosphorus tribromide (351 mg, 1.30 mmol) was added thereto while stirring through nitrogen gas, followed by further stirring at the same temperature for 30 minutes. Methanol was added to the reaction mixture, which was then washed with cold saturated aqueous sodium bicarbonate solution and cold brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give a colorless oil (609 mg, 95%). This material was so unstable that it was used for the next reaction without purification.

¹ H NMR (CDCl ₃ ): δ5.42 (t, J = 9Hz, 1H), 5.10 (broad signal, 1H) 3.97 (d, J = 2hZ, 2H) 2.05 (s, 4H) 1.69 (s, 6H) 1.60 (s, 3 H)

IR (Vmax, cm ^-1 ): 2950-3000, 1675, 1380

Example 5

Synthesis of Geranyl Phenyl Sulfone

Experimental Method: Dissolve geranyl bromide (500 mg, 2.303 mmol) in 5 ml anhydrous DMF in a 10 ml two-neck flask, add benzenesulfonic acid (sodium salt, 98%) (690 mg, 4.202 mmol), and add 20 mL of nitrogen. Stirred for hours. The reaction mixture was diluted with water and extracted twice with ether. The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography using ethyl acetate and hexane (1: 10) mixed solution to obtain a pale yellow oil (460 mg, 72%).

¹ H NMR (CDCl ₃ ): δ 7.85 (m, 2H) 7.50 (m, 3H) 4.8-5.33 (s, 2H) 3.75 (d, J = 8 Hz, 2H) 1.98 (m, 4H) 1.66 (s, 3H) 1.56 (s, 3H) 1.33 (s, 3H)

IR (Vmax, cm ^-1 ): 2970, 2870, 1440, 1380, 1310, 1140

Example 6

Synthesis of 6,10,14,18-tetramethyl-10 (phenylsulfonyl) -5,9,13,17-nonadecatetraen-2-one ethylene acetal

Test Method: Sodium hydride (60%) (48 mg, 1 mmol) was suspended in 7 ml of anhydrous DMF in a 25 ml two-necked flask, then cooled for ice and dissolved in 1 ml of anhydrous DMF while passing through a nitrogen stream. (278 mg, 1 mmol) is added. The ice bath was removed and stirred for 30 minutes. 11-Chloro-6,10dimenyl-5,9-undecadien-2-one ethylene acetal (273 mg, 1 mmol) was added to the reaction mixture, which was stirred at room temperature for 5 hours, followed by reaction with cooled 5% hydrochloric acid. Stopped and extracted three times with ether. The combined organic layer was washed twice with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a crude product. This crude product was purified by column chromatography with ethyl acetate-hexane (1: 4) mixed solution to obtain an oil (313 mg, 61%).

¹ H NMR (CDCl ₃ ): δ 7.86 (m, 2H) 7.54 (m, 3H) 4.90-5.33 (m, 4H) 3.96 (s, 4H) 3.70-4.13 (m, 1H) 1.90-2.23 (m, 14H) 1.70 (s, 6H) 1.61 (s, 6H) 1.36 (s, 3H) 1.26 (s, 3H)

IR (Vmax, cm ^-1 ): 2970, 2870, 1440, 1380, 1310, 1220, 1135

Example 7

Synthesis of 6,10,14,18-tetramethyl-5,9,13,17-nonadecatetraen-2-one ethylene acetal

Experimental Method: Dissolve 100 ml of two-necked flask of sulfone compound (514 mg, 1 mmol) and disodium hydrogen phosphate (568 mg, 4 mmol) in 50 ml of anhydrous methanol, and 6% sodium amalgam at -10 ° C through nitrogen stream. (1.5 g, 4 mmol) was added in one portion. The mixture was stirred at −10 ° C. for 20 minutes and then quenched with saturated aqueous ammonium chloride solution and extracted with ether. The combined organic layers were washed with saturated aqueous sodium bicarbonate solution, dried over anhydrous magnesium hydroxide, filtered and concentrated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography with 6% ethyl acetate-hexane mixed solution to give an oil (307 mg, 82%).

¹ H NMR (CDCl ₃ ): δ 5.02-5.18 (m, 4H) 4.00 (s, 4H) 1.98-2.26 (m, 16H) 1.68 (s, 3H) 1.58 (2, 12H), 1.33 (s, 3H )

IR (Vmax, cm ^-1 ): 2970, 2870, 1440, 1380, 1210, 1135, 950, 865

Example 8

Synthesis of 6,10,14,18-tetramethyl-5,9,13,17-nonadecatetraen-2-one

Experimental Method: 6,10,14,18-tetramethyl-5,9,13,17-nonadecatetraen-2-one ethylene acetal (420 mg, 1.033 mmol) was added to a 25 ml flask and refluxed for 3 hours. . The reaction mixture was diluted with water and extracted three times with dichloromethane. The combined organic layers were washed with water and brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography with ethyl acetate and benzene (2:98) mixed solution to give a colorless oil (323 mg, 98%).

¹ H NMR (CDCl ₃ ): δ 5.02-5.18 (m, 4H) 2.26-2.54 (m, 4H) 1.98-2.13 (m, 15H) 1.68-s, 3H) 1.60 (s, 12H)

IR (Vmax, cm ^-1 ): 1690, 1660, 1380

Example 9

Synthesis of 6-methyl-5 (E) -hepten-2-one ethylene acetal

Experimental Method: Dissolve 6-methyl-5 (E) -hepten-2-one (1.26 mg, 10 mmol) in 50 ml two-necked flask in anhydrous benzene (25 ml), and use ethylene glycol (0.87 g, 14 mmol) and p-toluenesulfonic acid. (5 mg) was added followed by a Dean-Stark trap, reflux cooler on it, and refluxed for 9 hours. After cooling the reaction mixture to room temperature, saturated aqueous sodium bicarbonate solution was added to separate the benzene layer, and the aqueous layer was extracted three times with petroleum ether. The combined organic layers were washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a crude product. This crude product was obtained by column chromatography on benzene to give an oil (1.55 g, 91%).

¹ H NMR (CDCl ₃ ): δ 4.90-5.30 (m, 1H) 3.92 (s, 4H) 2.20-2.50 (m, 4H) 1.70 (s, 3H) 1.63 (s, 3H) 1.30 (s, 3H)

IR (Vmax, cm ^-1 ): 2970, 1460, 1380, 1220, 1050

Example 10

Synthesis of 7-hydroxy-6-methyl-5 (E) -hepten-2-one ethylene acetal

Experimental method: Suspension of selenium dioxide (0.55g, 5mmol) in dichloromethane in a 200ml two-necked flask and add 70% t-butyl hydroperoxide (1.8g, 5mmol) while stirring for 30 minutes while blocking the light. 6-methyl-5 (E) -hepten-2-one ethylene acetal (1.7 g, 10 mmol) was added dropwise at 0 ° C. The reaction mixture is kept at 10 ° C., stirred for 5 hours and diluted with dichloromethane. The pale yellow diluent was washed with water and dilute aqueous sodium hydroxide solution, washed with water and brine again, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give a yellow oil. The yellow oil was dissolved in 25 ml of methanol, cooled using an ice bath, sodium borohydride (220 mg) was added and stirred at room temperature for 30 minutes. The solvent was evaporated under reduced pressure, the same amount of ether and water was added to the filtrate and then extracted three times with ether. The combined organic layers were washed with water and brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography using ethyl acetate and hexane (1: 4) mixed solution to obtain a colorless oil (1.36 g, 73%).

¹ H NMR (CDCl ₃ ): δ5.40 (t, J-7Hz, 1H), 3.97 (s, 2H), 3.92 (s, 4H) 2.10 (m, 2H) 1.60 (m, 2H) 1.65 (s, 3H) 1.30 (s, 3H)

IR (Vmax, cm ^-1 ): 3400 (broad peak), 2970, 2920, 2870, 1445, 1380, 1220, 1135, 1055, 950, 865

Example 11

Synthesis of 7-chloro-6-methyl-5 (E) -hepten-2-one ethylene acetal

Experimental Method: Put allyl alcohol (988 mg, 5.31 mmol) and 2,4,6-collidine (926 μl, 7.01 mmol) in a 10 ml flask, stir through a stream of nitrogen, and dissolve in a small amount of anhydrous DMF. (550 mg, 13 mmol) was added and cooled to 0 ° C. Methane sulfonyl chloride (566 µl) and 7.31 mmol) were added dropwise thereto, followed by stirring at the same temperature for 1 hour 30 minutes. Cooled water was added to the reaction mixture, and the aqueous layer was extracted three times with pentane. The combined organic layers were washed several times with water and saturated aqueous copper nitrate solution, and subsequently washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain an oil (1.012 g, 93%).

¹ H NMR (CDCl ₃ ): δ5.53 (t, J = 7.6Hz, 1H) 4.00 (s, 2H) 3.91 (s, 4H) 2.11 (m, 2H) 1.73 (s, 3H) 1.70 (m, 2H ) 1.31 (s, 3H)

IR (Vmax, cm ^-1 ): 2970, 2930, 2870, 1440, 1380, 1260, 1210, 1135, 1055, 940, 865, 685

Example 12

Synthesis of Farnesyl Bromide

Experimental method: In a 25 ml two-necked flask, farnesol (889 mg, 4 mmol) was dissolved in 4 ml of anhydrous hexane and cooled using an ice bath. Phosphorus tribromide (541 mg, 2 mmol) was added thereto while stirring through nitrogen gas, followed by further stirring at the same temperature for 30 minutes. Methanol was added to the reaction mixture, which was then washed with cold saturated aqueous sodium bicarbonate solution and cold brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give a colorless oil (1128 mg, 98.9%). This material was so unstable that it was used for the next reaction without purification.

¹ H NMR (CDCl ₃ ): δ 5.10-5.46 (m, 3H) 3.97 (d, J = 7Hz, 2H) 2.1 (brs, 8H) 1.6 and 1.7 (s, 12H)

IR (Vmax, cm ^-1 ): 1665, 1455, 1380, 1180

Example 13

Synthesis of Farnesyl Phenyl Sulfone

Experimental Method: Dissolve the particyl bromide (1.14g, 4mmol) in 11ml anhydrous DMF in 25ml two-necked flask, add benzenesulfonic acid (sodium salt, 98%) (1.2g, 7.3mmol) Stirred for hours. The reaction mixture was diluted with water and extracted twice with ether. The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography using ethyl acetate and hexane (1: 10) solution to give a pale yellow oil (1.12 g, 61%).

¹ H NMR (CDCl ₃ ): δ1.33 (3H, s) 1.60 (3H, s) 1.69 (6H, s) 2.0 (8H, broa) 3.80 (2H, j, J = 7Hz) 5.10 (2H, m) 5.20 (H, t, J = 7 Hz) 7.50 (3H, m) 7.85 (2H, m)

IR (Vmax, cm ^-1 ): 1450, 1305, 1160, 980

Example 14

Synthesis of 6,10,14,18-tetramethyl-6- (phenylsulfonyl) -5,9,13,17-nonadecatetraen-2-one ethylene acetal

Experimental Method: Sodium hydride (60%) (48 mg, 1 mmol) was suspended in 7 ml of anhydrous DMF in a 25 ml two-necked flask, cooled in an ice bath, and dissolved in 1 ml of anhydrous DMF while passing through a nitrogen stream. (346 mg, 1 mmol) is added. The ice bath was removed and stirred for 30 minutes. 7-Chloro-6-methyl-5-hepten-2-one ethylene acetal (205 mg, 1 mmol) was added to the reaction mixture, which was stirred for 5 hours at room temperature. The reaction was quenched with cooled 5% hydrochloric acid, followed by ether 3 Extracted twice. The combined organic layers were washed twice with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a crude product. This crude product was purified by column chromatography with ethyl acetate-hexane (1: 4) mixed solution to give an oil (324 mg, 63%).

¹ H NMR (CDCl ₃ ): δ 7.86 (m, 2H) 7.55 (m, 3H) 4.90-5.33 (m, 4H) 3.96 (s, 4H) 3.76-4.20 (m, 1H) 1.90-2.23 (m, 14H) 1.73 (s, 6H) 1.60 (s, 6H) 1.36 (s, 3H) 1.30 (s, 3H)

IR (Vmax, cm ^-1 ): 2970, 2920, 2870, 1440, 1380, 1310, 1220, 1140

Example 15

Synthesis of 6,10,14,18-tetramethyl-5,9,13,17-nonadecatetraen-2-one ethylene acetal

Experimental Method: Dissolve the sulfone compound (514 mg, 1 mmol) and disodium hydrogen phosphate (568 mg, 4 mmol) in 50 ml of anhydrous methanol in a 100 ml two-necked flask, and add 6% sodium at -10 ° C through a nitrogen stream. Mandarin (1.5 g, 4 mmol) was added at one time. The mixture was stirred at −10 ° C. for 20 minutes and then quenched with saturated aqueous ammonium chloride solution and extracted with ether. The combined organic layers were washed with saturated aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a crude product. The crude product 6% ethyl acetate-hexane mixed solution was obtained using oil column chromatography (307 mg, 82%).

¹ H NMR (CDCl ₃ ): δ 5.02-5.18 (m, 4H) 4.00 (s, 4H) 1.98-2.26 (m, 16H) 1.68 (s, 3H) 1.58 (s, 12H) 1.33 (s, 3H)

IR (Vmax, cm ^-1 ): 2970, 2870, 1440, 1380, 1210, 1135, 950, 865

Example 16

Synthesis of 6,10,14,18-tetramethyl-5,9,13,17-nonadecatetraen-2-one

Experimental Method: Dissolve 6,10,14,18-tetramethyl-5,9,13,17-nonadecateteten-2-one etal acetal (420 mg, 1.033 mmol) in a 25 ml flask in 5 ml of acetone. 50% phosphoric acid (0.41 ml, 7.241 mmol) was added and then refluxed for 3 hours. The reaction mixture was diluted with water and extracted three times with dichloromethane. The combined organic layers were washed with water and brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography with ethyl acetate and benzene (2: 98) mixed solution to give a colorless oil (323 mg, 98%).

¹ H NMR (CDCl ₃ ): δ 5.02-5.18 (m, 4H) 2.26-2.54 (m, 4H) 1.98-2.13 (m, 4H) 1.98-2.13 (m, 15H) 1.63 (s, 3H) 1.60 ( s, 12H)

IR (Vmax, cm ^-1 ): 1690, 1660, 1380

Claims (5)

The following compound of formula (4) is obtained by reacting the compound of formula (7) with the compound of formula (7) to treat the compound of formula (8) to produce the compound of formula (9). A process for preparing a compound of formula (I) by removing a protecting group from a compound. Wherein R is lower alkyl, benzene, toluene, m is 0 or 1, n is 1 or 2 (where n is 2 if m is 0 and n is 1 at the same time). It is an atom. A process for preparing the compound of formula (6) by treating the compound of formula (5) and sulfonating the compound of formula (6) to produce the compound of formula (7). Wherein R, n and X are as described above. A compound of formula (7), In the formula, R and n are as described above. The compound of formula (1) was treated with ethylene glycol to prepare a compound of formula (2), and the compound of formula (2) was oxidized to prepare a compound of formula (3). A process for preparing the compound of formula (4) by treating the compound of) with a halogenating agent. Wherein m and X are as described above. General formula (4) and a compound. Wherein m and X are as described above.