* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Stage #1: at 20℃; for 1 h; Stage #2: With hydrazine hydrate In butan-1-ol for 3 h; Reflux
General procedure: Adamantan-1-ylmethanol 1a-1d was added in portions over 5-10 min with vigorous stirring to fuming nitricacid at 15-20 °C. The resulting solution was vigorously stirred for 1 h at 20 °C and poured onto 500 g of crushed ice. The product was extracted into butan-1-ol (6 mL), the organic layer was separated, 20 mL of hydrazine hydrate was added, and the mixture was refluxed for 3 h. The mixture was cooled, diluted with 10 mL of butan-1-ol, and washed with water (2 ×20 mL), 5percent aqueous potassium hydroxide (3 × 15 mL), and water again (2 × 10 mL). The organic phase was dried and evaporated under reduced pressure, and the residue was recrystallized from toluene. The alkaline washings were acidified with aqueous HCl, and the precipitate of 3-hydroxyadamantane-1-carboxylic acid 5a-5d was filtered off. (3-Hydroxyadamantan-1-yl)methanol (4a) was synthesized from 2 g (0.012 mol) of 1a and 20 mL of fuming nitric acid. Yield 1.6 g (75percent), mp 140-142 °C; published data [50]: mp 139-141 °C. 3-Hydroxyadamantane-1-carboxylic acid (5a).Yield 0.18 g (8percent), mp 203-205 °C; published data [64]: mp 202-203 °C.
Reference：
[1] Russian Journal of Organic Chemistry, 2018, vol. 54, # 9, p. 1294 - 1300[2] Zh. Org. Khim., 2018, vol. 54, # 9, p. 1283 - 1289,8
2
[ 157774-23-7 ]
[ 38584-37-1 ]
Yield
Reaction Conditions
Operation in experiment
89%
With hydrazine hydrate In butan-1-ol for 3 h; Reflux
General procedure: A mixture of 0.5 g of dinitrate 2a-2d, 1 mL of butan-1-ol, and 3 mL of hydrazine hydrate was refluxed for 3 h. The resulting solution was cooled, diluted with 10 mL of water, and extracted with butan-1-ol (3 × 5 mL). The extract was washed with water and dried, the solvent was evaporated under reduced pressure, and the residue was recrystallized from toluene. Listed below are compound no., yield, and melting point: 4a, 89percent, 140-142 °C; 4b, 87percent, 127-129 °C; 4c, 88percent, 114-115 °C; 4d, 93percent, 137-138 °C.
Reference：
[1] Russian Journal of Organic Chemistry, 2018, vol. 54, # 9, p. 1294 - 1300[2] Zh. Org. Khim., 2018, vol. 54, # 9, p. 1283 - 1289,8
[3] Russian Journal of Organic Chemistry, 1993, vol. 29, # 7.1, p. 1126 - 1131[4] Zhurnal Organicheskoi Khimii, 1993, vol. 29, # 7, p. 1358 - 1364
3
[ 42711-75-1 ]
[ 38584-37-1 ]
Yield
Reaction Conditions
Operation in experiment
29.5 g
Stage #1: With sodium tetrahydroborate In tetrahydrofuran at 0 - 31℃; for 2.5 h; Stage #2: With boron trifluoride diethyl etherate In tetrahydrofuran at 0 - 30℃; for 14.5 h; Stage #3: With water In tetrahydrofuran at 0 - 10℃; for 1 h;
3-Hydroxytricyclo[3.3.1.13'7]decane-l-carboxylic acid obtained by Example 1 (Formula VIII; 25 g) was added to tetrahydrofuran (250 mL) at 31°C, cooled to 0°C, then sodium borohydride (6.3 g) was added at 0°C to 10°C over 30 minutes, the mixture was stirred for 2 hours at 28°C to 31°C, then cooled to 0°C. Boron trifluoride etherate (20.5 mL) was added to the reaction mixture over 30 minutes at 0°C to 2°C, the mixture was warmed to 30°C while stirring for 14 hours, then cooled to 0°C. Water (250 mL) was added for 1 hour at 0°C to 10°C, followed by the addition of ethyl acetate (200 mL) at 10°C. The pH of the reaction mixture was adjusted to 8 by using 25percent w/v aqueous sodium carbonate (40 mL), then the mixture was stirred for 15 minutes at 35°C to 38°C. The organic layer was stored and the aqueous layer was extracted twice with ethyl acetate (50 mL) at 35°C to 38°C. The organic layers were combined, washed with saturated brine solution (25 mL), and the solvents were recovered under reduced pressure at 45°C to 47°C to obtain the title compound. Yield: 29.5 g
Stage #1: at 20℃; for 1 h; Stage #2: With hydrazine hydrate In butan-1-ol for 3 h; Reflux
General procedure: Adamantan-1-ylmethanol 1a-1d was added in portions over 5-10 min with vigorous stirring to fuming nitricacid at 15-20 °C. The resulting solution was vigorously stirred for 1 h at 20 °C and poured onto 500 g of crushed ice. The product was extracted into butan-1-ol (6 mL), the organic layer was separated, 20 mL of hydrazine hydrate was added, and the mixture was refluxed for 3 h. The mixture was cooled, diluted with 10 mL of butan-1-ol, and washed with water (2 ×20 mL), 5percent aqueous potassium hydroxide (3 × 15 mL), and water again (2 × 10 mL). The organic phase was dried and evaporated under reduced pressure, and the residue was recrystallized from toluene. The alkaline washings were acidified with aqueous HCl, and the precipitate of 3-hydroxyadamantane-1-carboxylic acid 5a-5d was filtered off. (3-Hydroxyadamantan-1-yl)methanol (4a) was synthesized from 2 g (0.012 mol) of 1a and 20 mL of fuming nitric acid. Yield 1.6 g (75percent), mp 140-142 °C; published data [50]: mp 139-141 °C. 3-Hydroxyadamantane-1-carboxylic acid (5a).Yield 0.18 g (8percent), mp 203-205 °C; published data [64]: mp 202-203 °C.
Reference：
[1] Russian Journal of Organic Chemistry, 2018, vol. 54, # 9, p. 1294 - 1300[2] Zh. Org. Khim., 2018, vol. 54, # 9, p. 1283 - 1289,8
diphenylammonium trifluoromethanesulfonate; for 36h;Heating / reflux;
(2) 100 Parts of toluene, 10.0 parts of sodium salt of difluorosulfoacetic acid (purity: 97.6%), 8.98 parts of (3-hydroxy-1-adamantyl)methanol and 0.3 part of diphenylammonium trifluoromethanesulfonate were mixed. The mixture obtained was heated and refluxed for 36 hours. The mixture was cooled, and then, concentrated. To the residue obtained, 287 parts of acetonitrile was added, and the mixture obtained was stirred and filtrated. The filtrate obtained was concentrated. To the concentrated liquid obtained, 141 parts of tert-butyl methyl ether was added and the resultant mixture was stirred and filtrated to obtain the solid. The solid obtained was dried to obtain 16.7 parts of the salt represented by the above-mentioned formula (a) in the form of white green solid.
sulfuric acid; for 22h;Heating / reflux;Product distribution / selectivity;
(2) 5.0 Parts of the salt represented by the formula (g), 2.1 parts of (3-hydroxy-1-adamantyl)methanol, 50 parts of toluene and 0.3 part of concentrated sulfuric acid were mixed. The mixture obtained was heated and refluxed for 22 hours. The mixture was cooled, and then, concentrated. To the residue obtained, 90 parts of chloroform was added, and the solution obtained was repeated to wash with an ion-exchanged water until the aqueous layer obtained was neutralized. The organic layer obtained was concentrated and the residue obtained was mixed with 49 parts of ethyl acetate. The resultant mixture was stirred and filtrated to obtain the solid. The solid obtained was dried to obtain 5.4 parts of the salt represented by the above-mentioned formula (b). The 1H-NMR spectrum of the salt obtained was the same as that of the salt obtained in above-mentioned Salt Synthesis Example 1.
With hydrazine hydrate; In butan-1-ol; for 3h;Reflux;
General procedure: A mixture of 0.5 g of dinitrate 2a-2d, 1 mL of butan-1-ol, and 3 mL of hydrazine hydrate was refluxed for 3 h. The resulting solution was cooled, diluted with 10 mL of water, and extracted with butan-1-ol (3 × 5 mL). The extract was washed with water and dried, the solvent was evaporated under reduced pressure, and the residue was recrystallized from toluene. Listed below are compound no., yield, and melting point: 4a, 89%, 140-142 C; 4b, 87%, 127-129 C; 4c, 88%, 114-115 C; 4d, 93%, 137-138 C.
(2) 1.0 Part of 1,1'-carbonyldiimidazol was added to a mixture of 1.9 parts of sodium difluorosulfoacetate (purity: 62.7%) and 9.5 parts of N,N-dimethylformamide, and the added mixture was stirred for 2 hours to obtain solution (referred to as solution A). 0.2 Part of sodium hydride was added to a mixture of 1.1 parts of 3-hydroxyadamantylmethanol and 5.5 parts of N,N-dimethylfomamide, and the added mixture was stirred for 2 hours to obtain solution (referred to as solution B). The solution A was added to the solution B, and the mixture was stirred for 15 hours to obtain sodium salt of 3-hydroxy-1-adamantylmethyl difluorosulfoacetate solution. The sodium salt of 3-hydroxy-1-adamantylmethyl difluorosulfoacetate solution was used for the next step without further separation or purification.
1-hydroxy-3-(acryloyloxymethyl)adamantane[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90%
With triethylamine; In 1,4-dioxane;
(3) Esterification and polymerization A mixture of <strong>[38584-37-1]1-hydroxy-3-hydroxymethyladamantane</strong> (1 mmol), acryloyl chloride (1.2 mols), triethylamine (1.2 mols) and dioxane (10 ml) was stirred at 40C for 3 hours. As a result, 1-hydroxy-3-(acryloyloxymethyl)adamantane of the following formula was obtained (yield 90%).
And, as the result, the 1-carboxy-3-adamantanol was converted into a 1-hydroxymethyl-3-adamantanol (yield:95%) with a conversion of 99%.
29.5 g
3-Hydroxytricyclo[3.3.1.13'7]decane-l-carboxylic acid obtained by Example 1 (Formula VIII; 25 g) was added to tetrahydrofuran (250 mL) at 31C, cooled to 0C, then sodium borohydride (6.3 g) was added at 0C to 10C over 30 minutes, the mixture was stirred for 2 hours at 28C to 31C, then cooled to 0C. Boron trifluoride etherate (20.5 mL) was added to the reaction mixture over 30 minutes at 0C to 2C, the mixture was warmed to 30C while stirring for 14 hours, then cooled to 0C. Water (250 mL) was added for 1 hour at 0C to 10C, followed by the addition of ethyl acetate (200 mL) at 10C. The pH of the reaction mixture was adjusted to 8 by using 25% w/v aqueous sodium carbonate (40 mL), then the mixture was stirred for 15 minutes at 35C to 38C. The organic layer was stored and the aqueous layer was extracted twice with ethyl acetate (50 mL) at 35C to 38C. The organic layers were combined, washed with saturated brine solution (25 mL), and the solvents were recovered under reduced pressure at 45C to 47C to obtain the title compound. Yield: 29.5 g
(2) Reduction A mixture of 1-hydroxy-3-carboxyadamantane (2 mmols), sodium boron hydride (NaBH4) (6 mmols) and tetrahydrofuran (25 ml) was stirred at room temperature for 6 hours. As a result, 1-hydroxy-3-hydroxymethyladamantane was obtained (yield 90%).
1-hydroxymethyl-3-meyhacryloyloxyadamantane[ No CAS ]
[ 38584-37-1 ]
Yield
Reaction Conditions
Operation in experiment
90%
Example 23 The reaction was conducted in the same manner as in Example 4 except that 1.00 mmol of the 1-hydroxymethyl-3-adamantanol obtained by the method of Preparation Example 8 and 1.10 mmol of isopropenyl methacrylate were used instead of the adamantanediol, and, as a result, a 1-hydroxymethyl-3-meyhacryloyloxyadamantane was obtained with a yield of 90%.
To a mixture of 1.1 parts of a compound represented by the formula (H1-3) and 5.5 parts of N,N-dimethylformamide, 0.2 part of sodium hydride was added, and the resultant mixture was stirred for 2 hours. To the mixture obtained, the solution containing the salt represented by the formula (H1-2) was added. The resultant mixture was stirred for 15 hours to obtain a solution containing a salt represented by the formula (H1-4).
To a mixture of 100 parts of the compound represented by the formula (II-1) and 150 parts of ion-exchanged water,230 parts of a 30% sodium hydroxide aqueous solution was added dropwise.The resulting mixture was refluxed at 100 C. for 3 hours, cooled,This was neutralized with 88 parts of concentrated hydrochloric acid.The obtained solution was concentrated to obtain 164.4 parts (containing inorganic salt (NaCl), purity 62.7%) of a salt represented by the formula (H-2).To a mixture of 1.9 parts (purity 62.7%) of the salt represented by the formula (H-2) thus obtained and 9.5 parts of N, N-dimethylformamide, 1,1'-carbonyldiimidazole 1 . 0 part was added,And stirred for 2 hours to prepare a solution containing a salt represented by the formula (H-2). On the other hand, 0.2 part of sodium hydride was added to a mixture of 1.1 part of the compound represented by the formula (H-1) and 5.5 parts of N, N-dimethylformamide, and the mixture was stirred for 2 hours. To the obtained solution, a solution containing a salt represented by the above formula (H-2) was added. The resulting solution was stirred for 15 hours to obtain a solution containing a salt represented by the formula (H-3).
To a mixture of 100 parts of the compound represented by the formula (I-2-a) and 150 parts of ion-exchanged water, 230 parts of 30% sodium hydroxide aqueous solution was added dropwise in an ice bath. The resulting mixture was refluxed at 100 C. for 3 hours, after cooling, it was neutralized with 88 parts of concentrated hydrochloric acid. The resulting solution was concentrated to obtain 164.4 parts of a salt represented by the formula (I-2-b) (containing an inorganic salt (NaCl)Purity 62.7%).1.9 parts (62.7% purity) of the salt represented by the formula (I-2-b)And 9.5 parts of N, N-dimethylformamide,1.0 part of 1,1'-carbonyldiimidazole was added,And stirred for 2 hours to prepare a solution containing a salt represented by the formula (I-2-b).On the other hand, to a mixture of 1.1 parts of the compound represented by the formula (I-6-III) and 5.5 parts of N, N-dimethylformamide,0.2 part of sodium hydride was added and the mixture was stirred for 2 hours.To the obtained solution, a solution containing a salt represented by the above formula (I-2-b) was added.The resulting solution was stirred for 15 hours to obtain a solution containing a salt represented by the formula (I-2-c).
on the other hand 1.1 parts of 3-hydroxyadamantyl methanol and 1.1 parts of N, N-dimethylforma Mid, 0.2 part of sodium hydride was added and the mixture was stirred for 2 hours. To this solution the above mixture was added. The resulting mixture was stirred for 15 h, A solution containing the salt represented by the formula (I-DD-1-d) thus produced was directly used for the next reaction.
1.0 part of 1,1'-carbonyldiimidazole was added to 1.9 parts (purity 62.7%) of the resulting difluorosulfoacetic acid sodium salt and 9.5 parts of N, N-dimethylformamide, and the mixture was stirred for 2 hours.This solution was added to a solution of 1.1 parts of 3-hydroxyadamantylmethanol and 5.5 parts of N, N-dimethylformamide in 0.2 part of sodium hydride and stirred for 2 hours. After stirring for 15 hours, the resulting 1 - ((3-hydroxy-1-adamantyl) methoxycarbonyl) difluorosulfoacetic acid sodium salt was directly used in the next reaction.
A mixture of 5.06 parts of Salt (I-17), 1.82 parts of a compound represented by the formula (IV-1) and 50 parts of acetonitrile was stirred at 23 C. for 5 hours. The mixture was concentrated and then, 30 parts of chloroform and 15 parts of ion-exchanged water were added to the residue obtained. The mixture obtained was separated to obtain an organic layer. The organic layer was washed with 15 parts of ion-exchanged water and then, concentrated. The residue obtained was washed with 10 parts of tert-butyl methyl ether to obtain 5.33 parts of the salt represented by the above-mentioned formula (B1-18) in the form of white solid.Yield: 86% based on Salt (I-17)Yield: 86% based on the salt represented by the formula (II-3).
A mixture of 4.32 parts of Salt (I-25), 1.82 parts of a compound represented by the formula (IV-1) and 50 parts of acetonitrile was stirred at 23 C. for 5 hours. The mixture was concentrated and then, 30 parts of chloroform and 15 parts of ion-exchanged water were added to the residue obtained. The mixture obtained was separated to obtain an organic layer. The organic layer was washed with 15 parts of ion-exchanged water and then, concentrated. The residue obtained was dissolved in 20 parts of acetonitrile, and the solution obtained was concentrated. To the residue, 20 parts of ethyl acetate was added. The mixture obtained was concentrated.The residue obtained was mixed with 20 parts of tert-butyl methyl ether. The mixture obtained was stirred and then, the supernatant solution was removed. The residual layer was concentrated, and the residue obtained was mixed with 20 parts of ethyl acetate. The mixture obtained was stirred and the supernatant solution was removed. The residual layer was concentrated to obtain 4.27 parts of the salt represented by the formula (B1-20).Yield: 78% based on Salt (I-25)Yield: 78% based on the salt represented by the formula (II-4).
A mixture of 6.67 parts of Salt (I-33), 1.82 parts of a compound represented by the formula (IV-1) and 50 parts of acetonitrile was stirred at 23 C. for 5 hours. The mixture was concentrated and then, 30 parts of chloroform and 15 parts of ion-exchanged water were added to the residue obtained. The mixture obtained was separated to obtain an organic layer. The organic layer was washed with 15 parts of ion-exchanged water and then, concentrated. The residue obtained was dissolved in 20 parts of acetonitrile, and the solution obtained was concentrated. To the residue, 20 parts of ethyl acetate was added. The mixture obtained was concentrated.The residue obtained was mixed with 20 parts of tert-butyl methyl ether. The mixture obtained was stirred and then, the supernatant solution was removed. The residual layer was concentrated, and the residue obtained was mixed with 20 parts of ethyl acetate. The mixture obtained was stirred and the supernatant solution was removed. The residual layer was concentrated to obtain 6.42 parts of the salt represented by the formula (B1-26).Yield: 82% based on Salt (I-26)Yield: 75% based on the salt represented by the formula (B1-26-d)MS (ESI(+) Spectrum): M+ 263.1, MS (ESI(-) Spectrum): M- 517.2.
triphenylsulfonium 1-((3-hydroxy-1-adamantyl)methoxycarbonyl)difluoromethanesulfonate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80%
In acetonitrile; at 23℃; for 5h;
A mixture of 48.85 parts of Salt (I-9), 18.23 parts of a compound represented by the formula (IV-1) and 500 parts of acetonitrile was stirred at 23 C. for 5 hours. The mixture was concentrated and then, 300 parts of chloroform and 150 parts of ion-exchanged water were added to the residue obtained. The mixture obtained was separated to obtain an organic layer. The organic layer was washed with 150 parts of ion-exchanged water and then, concentrated. The residue obtained was washed with 100 parts of tert-butyl methyl ether to obtain 48.22 parts of the salt represented by the above-mentioned formula (B1-1) in the form of white solid.Yield: 80% based on Salt (I-9)Yield: 80% based on the salt represented by the formula (II-1).
In acetonitrile; at 23℃; for 5h;
488.5 parts of a salt represented by formula (I-2-b), 3- hydroxymethyl-adamantane-1 were charged 182.3 parts ol and 5000 parts of acetonitrile was stirred for 5 hours at 23 C.. The resulting mixture was concentrated, was added to 3000 parts of chloroform and 1500 parts of ion exchange water, by separatory operation, the organic layer was collected. After the collected organic layers were washed with 1500 parts of deionized water, and concentrating the obtained organic layer. The resulting concentrate was repulped with 1000 parts of tert- butyl methyl ether to obtain 482.2 parts of a salt represented by formula (I-2-c).
A mixture of 12.41 parts of Salt (I-1), 9.11 parts of a compound represented by the formula (IV-1) and 100 parts of acetonitrile was stirred at 23 C. for 5 hours. The mixture was filtrated to obtain 16.39 parts of the salt represented by the above-mentioned formula (V-2).Yield: 90% based on Salt (I-1)Yield: 85% based on the salt represented by the formula (II-2).
3-hydroxytricyclo[3.3.1.13'7]decane-1-carbaldehyde[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
11.5 g
With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hydrogencarbonate; potassium bromide; In dichloromethane; water; at 0 - 5℃;
3-(Hydroxymethyl)tricyclo[3.3.1.13'7]decan-l-ol as obtained by Example 2 (Formula VII; in-situ), was added to dichloromethane (250 mL), water (100 mL), potassium bromide (10 g), and sodium bicarbonate (11 g) at 30C. The obtained mixture was cooled to 0C, followed by the addition of TEMPO (0.02 g) and 10% w/v of sodium hypochlorite (230 mL) in portions at 0C to 5C. After completion of the reaction, the organic layer was stored and the aqueous layer was extracted with dichloromethane (50 mL). The organic layers were combined and washed with 10% w/v aqueous sodium thiosulphate (100 mL) and saturated brine solution (25 mL). The solvents were recovered under reduced pressure at 35C to 37C to obtain a yellowish solid (14 g). The obtained solid was dissolved in ethyl acetate (75 mL) and cooled to 15C. The organic layer was extracted with 10% w/v aqueous sodium bisulphite (100 mL). The aqueous layer was separated, added to ethyl acetate (75 mL), and cooled to 10C. The pH of the reaction mixture was adjusted to 10 by using a 25% w/v aqueous sodium hydroxide solution (30 mL) at 10C to 15C. The resulting mixture was stirred at 30C for 10 minutes. The organic layer was separated while the aqueous layer was extracted twice with ethyl acetate (25 ml). The organic layers were combined and solvents were recovered under reduced pressure at 45C to 47C to obtain the title compound. Yield: 11.5 g
With samarium(III) chloride hexahydrate; 4-methoxy-phenol; In chloroform; at 65℃; for 24h;
Compound (I-4-b) 1.79 parts of a 0.83 parts 3-hydroxyadamantyl methanol and chloroform 15.00 parts, addition of p- methoxyphenol 0.01g, the samarium chloride hexahydrate 0.09g and it was stirred for 24 hours at 65 C.The resulting mixture was charged with chloroform 10.0 parts of ion-exchanged water 10.0 parts, to recover the organic layer was separated. Concentrating the recovered organic layer was stirred with 10 parts of ethyl acetate to remove the supernatant. The resulting mixed with 10 parts of tert- butyl methyl ether to the residue and stirred to remove the supernatant. The resulting residue was dissolved in chloroform, and concentrated, the compound (I-4) was obtained 0.33 parts. The compound (I-4) was set to A4.
With samarium(III) chloride hexahydrate; 4-methoxy-phenol; In chloroform; at 65℃; for 24h;
Compound (I-1-b) 1.61 parts of a 0.83 parts 3-hydroxyadamantyl methanol and chloroform 15.00 parts, addition of p- methoxyphenol 0.01g, the samarium chloride hexahydrate 0.09g and it was stirred for 24 hours at 65 C. The resulting mixture was charged with chloroform 10.0 parts of ion-exchanged water 10.0 parts, to recover the organic layer was separated. Concentrating the recovered organic layer was stirred with 10 parts of ethyl acetate to remove the supernatant. The resulting mixed with 10 parts of tert- butyl methyl ether to the residue and stirred to remove the supernatant. The resulting residue was dissolved in chloroform, as orange oily product was concentrated to give the compound (I-1) was obtained 0.42 parts. Compound (I-1) was A1.
Compounds 2.55 parts represented by the formula (B5-b), was charged with compound 0.69 parts represented by dimethylformamide 20.00 parts of formula (B5-c), and stirred for 30 min at 23 CThey were charged 0.05 parts of potassium carbonate, and stirred for 2 hours at 23 C.. To the reaction product obtained, charged with 30 parts of chloroform and 10 parts of ion-exchanged water, it was performed stirring, a separation. Washing with water was carried out six times. They were charged 0.60 parts of activated carbon to the obtained organic layer, and stirred for 30 min at 23 C., and filtered. The filtrate was concentrated, the resulting concentrate was dissolved by adding 10 parts of acetonitrile, and concentrated. Then, this was stirred with 30 parts of tert- butyl methyl ether to remove the supernatant. The resulting residue was dissolved in chloroform, and concentrated. The resulting concentrate was purified by column (Merck silica gel 60-200 mesh developing solvent: chloroform / methanol = 5/1) by preparative fraction to give 1.12 parts of the salt represented by the formula (B5).
(3-hydroxyadamantane 1-ylmethyl)oxycarbonyl(difluoro)methanesulfonyl fluoride[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
73%
With triethylamine; In dichloromethane; at 0 - 20℃; for 4.5h;Large scale;
In a 10 L four-necked flask equipped with a stirrer, dropping funnel, thermometer,1002 g (5.50 mol) of 3- (hydroxymethyl) -1-adamantanol and 3711 g of dichloromethane were charged and cooled to 0 C. While maintaining the temperature at 0 to 10 C., 1089 g (6.05 mol) of 2- (fluorosulfonyl) difluoroacetyl fluoride was added dropwise from the dropping funnel over 4 hours. After the addition, the reaction solution was stirred for 30 minutes at around room temperature. After disappearance of raw materials was confirmed by 19 F-NMR measurement, the reaction solution was washed with 4950 g of water, and the obtained organic layer was concentrated at 40 C. under reduced pressure to obtain 1377 g (yield: 73%) of the objective ester .
(3-hydroxyadamantane 1-ylmethyl)oxycarbonyl(difluoro)methanesulfonyl fluoride[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With titanium(IV) isopropylate; In methanol; chloroform; at 23 - 63℃; for 6.5h;
40.00 parts of the compound represented by the formula (H-1) and 240 parts of chloroform were mixed and stirred at 23 C. for 30 minutes. 46.38 parts of the compound represented by the formula (II-1) and 1.25 parts of titanium isopropoxide were added to the obtained mixed solution,Methanol was distilled off while refluxing at 63 C. for 6 hours.12.50 parts of silica gel was added to the obtained reaction product, followed by stirring, followed by filtration. After concentration of the obtained filtrate, 300 parts of n-heptane was added to the concentrate, and then the concentrate was concentrated. 100 parts of n-heptane was added to the obtained concentrate, and the mixture was stirred at 23 C. for 6 hours and then filtered to obtain a compound represented by the formula (II-2)69.47 parts were obtained.
230 parts of 30% sodium hydroxide aqueous solution was added dropwise to 100 parts of difluoro(fluorosulfonyl)acetic acid methyl ester and 150 parts of ion-exchanged water in an ice bath. The resulting mixture was refluxed at 100 C for 3 hours, cooled to 23 C and neutralized with 88 parts of concentrated hydrochloric acid. The resulting mixture was concentrated to obtain 164.4 parts of sodium difluorosulfoacetate (containing inorganic salt, purity 62.7%). 1.9 parts of the obtained difluorosulfoacetic acid sodium salt (Purity 62.7%) and 9.5 parts of N,N-dimethylformamide, 1.0 part of 1,1'-carbonyldiimidazole was added and the mixture was stirred for 2 hours to prepare a mixture. On the other hand, 0.2 part of sodium hydride was added to 1.1 parts of 3-hydroxyadamantyl methanol and 5.5 parts of N,N-dimethylformamide, and the mixture was stirred for 2 hours. To this solution the above mixture was added. The resulting mixture was stirred for 15 hours and the resulting solution containing the sodium salt of difluorosulfoacetic acid 3-hydroxy-1-adamantyl methyl ester (I-5-c) was used as such in the subsequent reaction.
triphenylsulfonium 1-((3-hydroxy-1-adamantyl)methoxycarbonyl)difluoromethanesulfonate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With tetramethoxytitanium; In chloroform; at 23 - 65℃; for 24h;
6.93 parts of the salt represented by the formula (I-2-II), 4.19 parts of the compound represented by the formula (I-2-III) and 35.00 parts of chloroform were charged and stirred at 23 C. for 30 minutes did.To the resulting mixed solution, 0.53 parts (purity 95%) of titanium (IV) methoxide was charged,Reflux at 65 C for 24 hoursAfter removing methanol, the obtained reaction mass was cooled and filtered.After collecting the recovered filtrate,To the resulting residue, 105.00 parts of chloroform was added and dissolved.5.00 parts of silica gel and 0.17 part of 35% hydrochloric acid were charged in the obtained chloroform solution,After stirring at 23 C. for 1 hour, filtration was carried out.To the recovered filtrate, 40 parts of ion exchanged water was added and stirredAfter stirring, the mixture was separated, and the organic layer was recovered. This washing was carried out five times. To the obtained organic layer, activated carbon 1.0, And the mixture was stirred at 23 C. for 1 hour and then filtered. The collected filtrate was concentrated, concentrated20 parts of acetonitrile was added to the condensate, and the mixture was concentrated. To the obtained concentrate, ethyl acetate 35.24 parts of tert-butyl methyl ether and 35.24 parts of tert-butyl methyl ether were added, stirred and filtered7.30 parts of the salt represented by the formula (I-2) (the compound represented by the formula (I-2-a)A yield of 51% based on the compound, and a yield of 79% based on the salt represented by the formula (I-2-II)).The concentration of Ti contained in the salt represented by the formula (I-2) is also 160 ppb and there was no problem with the remnant of the metal.
With tetramethoxytitanium; In chloroform; at 23 - 65℃; for 24h;
7.92 parts of the salt represented by the formula (I-3-II), 4.38 parts of the compound represented by the formula (I-3-III) and 40.00 parts of chloroform were charged and stirred at 23 C. for 30 minutes did.To the obtained mixed solution,0.55 parts (purity 95%) of titanium (IV) methoxide was charged,Reflux at 65 C for 24 hoursAfter removing methanol,The resulting reaction mass was cooled and filtered.After collecting the recovered filtrate, 120.00 parts of chloroform was added to the obtained residue and dissolved.To the resulting chloroform solution,6.00 parts of silica gel and 0.20 part of 35% hydrochloric acid were charged, Stirred at 23 C. for 1 hour and then filtered.50 parts of ion-exchanged water was added to the recovered filtrate, followed by stirring,The organic layer was recovered. This washing was carried out five times.2.00 parts of activated carbon was charged in the obtained organic layer,After stirring at 23 C. for 1 hour, filtration was carried out.After collecting the recovered filtrate,20 parts of acetonitrile was added to the concentrate and then concentrated.To the obtained concentrate, 41.90 parts of ethyl acetate and 41.90 parts of tert-butyl methyl ether were added,After stirring, the mixture was filtered to obtain 8.40 parts of the salt represented by the formula (I-3) (yield: 79% based on the salt represented by the formula (I-3-II)).Incidentally, the Ti concentration contained in the salt represented by the formula (I-3) was also 150 ppb and there was no problem with the remnant of the metal.
With tetramethoxytitanium; In chloroform; at 23 - 65℃; for 24h;
9.04 parts of the salt represented by the formula (I-5-II), 4.38 parts of the compound represented by the formula (I-5-III) and 40 parts of chloroform were charged and stirred at 23 C. for 30 minutes. 0.55 parts (purity 95%) of titanium (IV) methoxide was charged in the resulting mixed solution, and the mixture was refluxed and de-methanolated at 65 C. for 24 hours, and the obtained reaction mass was cooled and filtered. After collecting the recovered filtrate, 120 parts of chloroform was added to and dissolved in the obtained residue.To the resulting chloroform solution, 6.00 parts of silica gel and 0.20 part of 35% hydrochloric acid were charged and stirred at 23 C. for 1 hour and then filtered. 50 parts of ion exchanged water was added to the recovered filtrate, and the mixture was stirred and separated, and the organic layer was recovered. This washing was carried out five times. 2.00 parts of activated carbon was charged in the obtained organic layer, stirred at 23 C. for 1 hour, and then filtered. After collecting the recovered filtrate, 20 parts of acetonitrile was added to the concentrate and then concentrated. 50 parts of ethyl acetate and 50 parts of tert-butyl methyl ether were added to the obtained concentrate, and the mixture was stirred and filtered to obtain 8.68 parts of a salt represented by the formula (I-5) (formula -5 - II) was obtained in a yield of 76%). Incidentally, the Ti concentration contained in the salt represented by the formula (I-5) was also 100 ppb and there was no problem with the remaining metal.
(3-hydroxyadamantan-1-yl)methyl 5-bromo-4,4,5,5-tetrafluoropentanoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
60 g
With pyridine; In acetonitrile; at 20℃; for 4h;
This example describes the synthesis of three inventive monomers. The synthetic sequence of the monomer indicated TBPDBT ADMA-TFPS is summarized in Figure 1.To a solution of 4-bromo-4,4,5,5-tetrafluoropentanoic acid (20 g, 158.1 mmol), N, N-dimethylformamide36 mmol) in 200 mL of acetonitrile was added oxalyl chloride (20 g, 157.57 mmol) dropwise.The mixture was stirred at room temperature for 2 hours and then added dropwise to a solution made of 150 mL of acetonitrile containing pyridine (12.4 g, 156.76 mmol) and 3-hydroxyadamantanemethanol (Compound 3; 28.8 g, 158.01 mmol).The mixture was stirred for 4 hours at room temperature, then the solvent was completely distilled off under reduced pressure and the resulting residue was dissolved in 200 mL of dichloromethane and washed twice with 200 mL of 0.1 N hydrochloric acid and then twice with 200 mL of deionized water.The organic phase is dried over MgSO4, filtered, and the solvent is removed completely to give the crude product as a colorless oil3-hydroxyadamantan-1-yl) methyl 5-bromo-4,4,5,5-tetrafluoropentanoate(Compound 4, 60 g) which was used in the next step without further purification.
2000 parts of the compound represented by the formula (I-20-1), 140.00 parts of chloroform and 19.57 parts of the compound represented by the formula (I-20-2) were charged and stirred at 23 C. for 1 hour. To the obtained reaction product, 50 parts of ion-exchanged water was charged and stirred and separated. Washed with water 5 times. 1.00 parts of activated carbon was charged in the obtained organic layer, stirred at 23 C. for 30 minutes, and filtered. The filtrate was concentrated. To the obtained concentrate, 100 parts of tert-butyl methyl ether was added, followed by stirring and filtration to obtain 24.94 parts of a salt represented by the formula (I-20-3).
With potassium carbonate; In N,N-dimethyl-formamide; at 23℃; for 2.5h;
5.80 parts of the compound represented by the formula (I-2), 30 parts of dimethylformamide and 1.37 parts of the compound represented by the formula (I-19-1) were charged and stirred at 23 C. for 30 minutes, 0.10 parts of potassium carbonate were charged, and the mixture was stirred at 23 C. for 2 hours. To the obtained reaction product, 60 parts of chloroform and 20 parts of ion-exchanged water were charged and stirred and separated. Washed with water six times. 1.00 parts of activated carbon was charged in the obtained organic layer, stirred at 23 C. for 30 minutes, and filtered. The filtrate was concentrated, 20 parts of acetonitrile was added to the concentrate, dissolved, and concentrated. Thereafter, 50 parts of tert-butyl methyl ether was added thereto, followed by stirring, and the supernatant was removed. The obtained residue was dissolved in chloroform and concentrated to obtain 5.88 parts of a salt represented by the formula (I-19-2).
FIG. 1 presents a chemical scheme for the synthesis of the photoacid generator compound referred to as TPS NE-AdOR-DFES. The synthesis process was as follows. To a suspension of 5 -norbomene-2,3 -dicarboxylicanhydride (20 grams, 122 millimoles) and 3-(hydroxymethyDadaman- tan-i-ol (22.2 grams, 121.8 millimoles) in acetonitrile (150 milliliters) was added N,N-dimethylaminopyridine (1.5 grams, 12.27 millimoles) and the reaction mixture was stirred at 65 C. for 18 hours. The mixture was cooled to room temperature and concentrated aqueous hydrochloric acid was added until the pR was reduced to 2. The crude product was filtered and dried, before being suspended in ethyl acetate (150 milliliters) and stirred for 30 minutes at room temperature. Filtration produced 28 grams (yield:66%) of pure product (1) as a white solid. ?R NMR (acetone-d6) oe: 6.22 (m, 1R), 6.17 (m 1R), 3.69 (d, 2R), 3.53 (d, 2R), 3.40 (m, 2R), 3.14 (m, 2R), 2.17 (s, 2R), 1.41-i. 67(m, 15R).
5 parts of the compound represented by the formula (I-1-a)Compound of formula (I-5-b) 13.59Part and 50 parts of chloroform were mixed,Followed by stirring at 23 C. for 30 minutes.To the obtained mixed solution, 0.73 part of sulfuric acid was added, and in the presence of molecular sieves,Followed by stirring at 60 C. for 10 hours. The resulting reaction mixture was cooled to 23 C.,150 parts of ion-exchanged water was added and 30After stirring for a minute, filtration was carried out,The recovered filtrate was separated and the organic layer was taken out. To the recovered organic layer,After adding 50 parts of 5% aqueous solution of sodium hydrogen carbonate and stirring at 23 C. for 30 minutes,The liquid was separated and the organic layer was taken out.50 parts of ion-exchanged water was added to the recovered organic layer, and the mixture was stirred at 23 C. for 30 minutes,The liquid was separated and the organic layer was taken out.After concentrating the recovered organic layer, to the concentrated mass,60 parts of n-heptane was added,After stirring at 23 C. for 30 minutes,By filtration, the compound of formula (I-5-c)To obtain 8.98 parts of a compound represented by the following formula.
1.99 parts of a salt represented by the formula (I-1-d) and 20 parts of chloroform were mixed,Followed by stirring at 23 C. for 30 minutes.To the obtained mixed solution,Compound represented by formula (I-1-e) 0.88Part, and the mixture was further stirred at 50 C. for 2 hours. After cooling the resultant reaction mixture to 23 C.,2.11 parts of the compound represented by the formula (I-5-c) was added, and further stirred at 23 C. for 18 hours.To the obtained reaction product, 5% oxalic acid aqueous solution 20Part was added and stirred at 23 C. for 30 minutes,The liquid was separated and the organic layer was taken out.20 parts of ion-exchanged water was added to the recovered organic layer, and the mixture was stirred at 23 C. for 30 minutes,The liquid was separated and the organic layer was taken out.This washing operation was repeated 5 times.After concentrating the recovered organic layer, to the concentrated residue,0.96 parts of acetonitrile and 28.68 parts of tert-butyl methyl ether were added,After stirring at 23 C. for 30 minutes,The supernatant was removed and concentrated,To obtain 2.23 parts of a salt represented by the formula (I-5).
5.00 parts of a salt represented by the formula (I-1-c)30 parts of chloroform and 1.18 parts of carbonyl diimidazole were mixed,Followed by stirring at 23 C. for 30 minutes. To the obtained mixed solution,1.46 parts of the compound represented by the formula (I-15-a) was added,Followed by stirring at 23 C. for 18 hours. To the obtained reaction product,30 parts of a 5% oxalic acid aqueous solution was added and stirred at 23 C. for 30 minutes,The liquid was separated and the organic layer was taken out.20 parts of ion-exchanged water was added to the recovered organic layer, and the mixture was stirred at 23 C. for 30 minutes, then separated, and the organic layer was taken out. This washing operation was repeated 5 times.After concentrating the recovered organic layer, to the concentrated mass,1 part of acetonitrile and 45 parts of tert-butyl methyl ether were added and stirred at 23 C. for 30 minutes, then the supernatant liquid was removed,By concentrating, a compound of the formula (I-15)To obtain 2.68 parts of the salt.
General procedure: Adamantan-1-ylmethanol 1a-1d was added in portions over 5-10 min with vigorous stirring to fuming nitricacid at 15-20 C. The resulting solution was vigorously stirred for 1 h at 20 C and poured onto 500 g of crushed ice. The product was extracted into butan-1-ol (6 mL), the organic layer was separated, 20 mL of hydrazine hydrate was added, and the mixture was refluxed for 3 h. The mixture was cooled, diluted with 10 mL of butan-1-ol, and washed with water (2 ×20 mL), 5% aqueous potassium hydroxide (3 × 15 mL), and water again (2 × 10 mL). The organic phase was dried and evaporated under reduced pressure, and the residue was recrystallized from toluene. The alkaline washings were acidified with aqueous HCl, and the precipitate of 3-hydroxyadamantane-1-carboxylic acid 5a-5d was filtered off. (3-Hydroxyadamantan-1-yl)methanol (4a) was synthesized from 2 g (0.012 mol) of 1a and 20 mL of fuming nitric acid. Yield 1.6 g (75%), mp 140-142 C; published data [50]: mp 139-141 C. 3-Hydroxyadamantane-1-carboxylic acid (5a).Yield 0.18 g (8%), mp 203-205 C; published data [64]: mp 202-203 C.
In the reactor, 60 parts of a compound represented by the formula (I-7-a)200 parts of tetrahydrofuran and 31.17 parts of pyridine were mixed and stirred at 23 for 30 minutes, and then cooled to 5 .To the obtained mixture,42.35 parts of the compound represented by the formula (I-1-b) was added and then stirred at 23 DEG C for 18 hours.To the reaction mixture, 350 parts of ethyl acetate and 275 parts of 10% aqueous potassium carbonate solution were added and then stirred at 23 DEG C for 30 minutes. The resulting organic layer was then collected therefrom.To the collected organic layer was added 300 parts of ion-exchanged water and after stirring for 30 minutes at 23 DEG C for washing, the organic layer was separated. The organic layer was washed 4 times with water in the same manner as mentioned above.The resulting mixture was then concentrated and the concentrate was purified by silica gel column chromatography [silica gel 60N (spherical, neutral), 100-210 mum , Kanto Chemical, eluent: n-heptane / ethyl acetate = 1/1] To obtain 58.11 parts of a compound represented by the formula (I-7-c).
7.90 parts of a salt represented by the formula (I-12-b) and 30 parts of chloroform were mixed and stirred at 23 C. for 30 minutes. 1.78 parts of the compound represented by the formula (I-3-b) was added to the obtained mixed solution, and the mixture was further stirred at 50 C. for 2 hours and then cooled to 23 C. 1.82 parts of the compound represented by the formula (I-3-f) was added to the obtained mixed solution, and the mixture was further stirred at 23 C. for 18 hours. To the obtained mixture, 15 parts of 5% oxalic acid aqueous solution was added and the mixture was stirred at 23 C. for 30 minutes, then separated, and the organic layer was taken out. 15 parts of ion-exchanged water was added to the obtained organic layer, and the mixture was stirred at 23 C. for 30 minutes, then separated, and the organic layer was taken out. This washing operation was repeated 5 times. After filtration of the obtained organic layer, the filtrate was concentrated, 30 parts of tert-butyl methyl ether was added to the concentrated residue, stirred at 23 C. for 30 minutes, the supernatant was removed and concentrated, 7.49 parts of a salt represented by the formula (I-12) was obtained.
5.82 parts of the salt represented by the formula (I-3-e) and 30 parts of chloroform were mixed and stirred at 23 C. for 30 minutes. To the obtained mixed solution,1.78 parts of the compound represented by the formula (I-3-b) was added,Further, after stirring at 50 C. for 2 hours, it was cooled to 23 C.To the obtained mixed solution, a compound represented by the formula (I-3-f)1.82 parts were added, and the mixture was further stirred at 23 C. for 18 hours.To the obtained mixture, 15 parts of 5% oxalic acid aqueous solution was added and the mixture was stirred at 23 C. for 30 minutes, then separated, and the organic layer was taken out.15 parts of ion-exchanged water was added to the obtained organic layer, and the mixture was stirred at 23 C. for 30 minutes, then separated, and the organic layer was taken out. This washing operation was repeated 5 times. After filtering the obtained organic layer, the filtrate was concentrated,To the concentrated residue, 30 parts of tert-butyl methyl ether was added,After stirring at 23 C. for 30 minutes, the supernatant was removed, And concentrated to obtain 6.12 parts of a salt represented by the formula (I-3)
60 parts of a compound represented by the formula (I-11-a), 200 parts of tetrahydrofuran and 31.17 parts of pyridine were mixed, stirred at 23 C. for 30 minutes, and cooled to 5 C. After 42.35 parts of a compound represented by the formula (I-1-b) was added to the obtained mixed solution, the temperature was raised to 23 C., and the mixture was stirred at 23 C. for 18 hours. After adding 350 parts of ethyl acetate and 275 parts of 10% potassium carbonate aqueous solution to the obtained reaction mixture and stirring for 30 minutes at 23 C., the layers are separated to separate an organic layer.It went out. 300 parts of ion-exchanged water was added to the obtained organic layer, and after stirring for 30 minutes at 23 C., the layers were separated to take out the organic layer. This water washing operation was repeated four times. The obtained organic layer is concentrated, and the concentrated mixture is subjected to column chromatography (silica gel 60 N (spherical, neutral) 100 to 210 mum; Kanto Chemical Co., Ltd. product, developing solvent: n-heptane / ethyl acetate = 1/1). By using and fractionating, 58.11 parts of a compound represented by the formula (I-11-c) was obtained.
Stage #1: Diphenyliodonium-2-carboxylate With methanesulfonic acid In N,N-dimethyl-formamide at 23 - 70℃; for 1.5h;
Stage #2: 1-hydroxy-3-hydroxymethyladamantane In N,N-dimethyl-formamide at 70℃; for 1h;
Stage #3: C16H18F6O7S*C6H15N In N,N-dimethyl-formamide at 23℃; for 1h;
7 Synthesis of salt represented by formula (I-187)
1.00 parts of the salt represented by the formula (I-3-a), 0.33 parts of methanesulfonic acid and 3 parts of dimethylformamide were mixed, stirred at 23 ° C. for 30 minutes, and then further at 70 ° C. for 1 hour. Stirred. To the obtained mixed solution, 0.80 part of the compound represented by the formula (I-177-b) was added, and the mixture was stirred at 70 ° C. for 1 hour and then cooled to 23 ° C. To the obtained mixed solution, 1.47 parts of a salt represented by the formula (I-13-c) was added, and the mixture was stirred at 23 ° C. for 1 hour, and then 30 parts of chloroform.Two parts of a 5% aqueous oxalic acid solution and 10 parts of ion-exchanged water were added, and the mixture was stirred at 23 ° C. for 30 minutes and separated to remove the organic layer. After adding 10 parts of ion-exchanged water to the obtained organic layer and stirring at 23 ° C. for 30 minutes, the solution was separated and the organic layer was taken out. This washing operation was repeated 3 times. The obtained organic layer is concentrated, and the concentrated mass is separated by a column (silica gel 60N (spherical, neutral) 100-210 μm; manufactured by Kanto Chemical Co., Inc., developing solvent: chloroform / methanol = 1/1). 0.18 parts of the salt represented by the formula (I-187) was obtained.
4-oxoadamantane 1-yl-oxycarbonyl(difluoro)methanesulfonate triethylamine[ No CAS ]
[ 1488-42-2 ]
C12H13F2O6S(1-)*C24H26IO3(1+)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Stage #1: Diphenyliodonium-2-carboxylate With methanesulfonic acid In N,N-dimethyl-formamide at 23 - 70℃; for 1.5h;
Stage #2: 1-hydroxy-3-hydroxymethyladamantane In N,N-dimethyl-formamide at 70℃; for 1h;
Stage #3: 4-oxoadamantane 1-yl-oxycarbonyl(difluoro)methanesulfonate triethylamine In N,N-dimethyl-formamide at 23℃; for 1h;
2 Synthesis of salt represented by formula (I-177)
1.00 parts of the salt represented by the formula (I-3-a), 0.33 parts of methanesulfonic acid and 3 parts of dimethylformamide were mixed, stirred at 23 ° C. for 30 minutes, and then further at 70 ° C. for 1 hour. Stirred. To the obtained mixed solution, 0.80 part of the compound represented by the formula (I-177-b) was added, and the mixture was stirred at 70 ° C. for 1 hour and then cooled to 23 ° C. To the obtained mixed solution, 1.10 parts of a salt represented by the formula (I-3-c) was added, and after stirring at 23 ° C. for 1 hour, 30 parts of chloroform and 2 parts of a 5% aqueous oxalic acid solution and ions were added. 10 parts of exchanged water was added, and the mixture was stirred at 23 ° C. for 30 minutes, separated, and the organic layer was taken out. After adding 10 parts of ion-exchanged water to the obtained organic layer and stirring at 23 ° C. for 30 minutes, the solution was separated and the organic layer was taken out. This washing operation was repeated 3 times. After concentrating the obtained organic layer, 10 parts of tert-butyl methyl ether was added to the concentrated residue, and the mixture was stirred at 23 ° C. for 30 minutes, and then the supernatant was removed and concentrated to obtain the formula (I-177). ) Was obtained.
Stage #1: Diphenyliodonium-2-carboxylate With methanesulfonic acid In N,N-dimethyl-formamide at 23 - 70℃; for 1.5h;
Stage #2: 1-hydroxy-3-hydroxymethyladamantane In N,N-dimethyl-formamide at 70℃; for 1h;
Stage #3: C23H27F2O9S(1-)*C7H11N2(1+) In N,N-dimethyl-formamide at 23℃; for 1h;
6 Synthesis of salt represented by formula (I-61)
1.00 parts of the salt represented by the formula (I-3-a), 0.33 parts of methanesulfonic acid and 3 parts of dimethylformamide were mixed, stirred at 23 ° C. for 30 minutes, and then further at 70 ° C. for 1 hour. Stirred. 0.73 parts of the compound represented by the formula (I-61-b) was added to the obtained mixed solution, and the mixture was stirred at 70 ° C. for 1 hour and then cooled to 23 ° C. To the obtained mixed solution, 1.10 parts of a salt represented by the formula (I-3-c) was added, and after stirring at 23 ° C. for 1 hour, 30 parts of chloroform and 2 parts of a 5% aqueous oxalic acid solution and ions were added. 10 parts of exchanged water was added, and the mixture was stirred at 23 ° C. for 30 minutes, separated, and the organic layer was taken out. After adding 10 parts of ion-exchanged water to the obtained organic layer and stirring at 23 ° C. for 30 minutes, the solution was separated and the organic layer was taken out. This washing operation was repeated 3 times. Obtained organicThe layer is concentrated, and the concentrated mass is separated by a column (silica gel 60N (spherical, neutral) 100-210 μm; manufactured by Kanto Chemical Co., Inc., developing solvent: chloroform / methanol = 1/1) to formulate (I-). 0.15 parts of the salt represented by 61) was obtained.
Stage #1: methanesulfonic acid; Diphenyliodonium-2-carboxylate In N,N-dimethyl-formamide at 23 - 70℃; for 1.5h;
Stage #2: 1-hydroxy-3-hydroxymethyladamantane In N,N-dimethyl-formamide at 70℃; for 1h;
Stage #3: C12H15F2O5S(1-)*C6H16N(1+) In N,N-dimethyl-formamide at 23℃; for 1h;
7 Example 7: Synthesis of salt represented by formula (I-786)
1.00 parts of the salt represented by the formula (I-438-a), 0.33 parts of methanesulfonic acid and 3 parts of dimethylformamide were mixed, stirred at 23 ° C. for 30 minutes, and then further at 70 ° C. for 1 hour. Stirred. To the obtained mixed solution, 0.80 part of the compound represented by the formula (I-786-b) was added, and the mixture was stirred at 70 ° C. for 1 hour and then cooled to 23 ° C. To the obtained mixed solution, 1.10 parts of a salt represented by the formula (I-177-d) was added, and after stirring at 23 ° C. for 1 hour, 30 parts of chloroform and 2 parts of a 5% aqueous oxalic acid solution and ions were added. 10 parts of exchanged water was added, and the mixture was stirred at 23 ° C. for 30 minutes, separated to remove the organic layer. After adding 10 parts of ion-exchanged water to the obtained organic layer and stirring at 23 ° C. for 30 minutes, the liquid was separated and the organic layer was taken out. This washing operation was repeated 3 times. After concentrating the obtained organic layer, 10 parts of tert-butyl methyl ether was added to the concentrated residue, and the mixture was stirred at 23 ° C. for 30 minutes, and then the supernatant was removed and concentrated to obtain the formula (I-786). ) Was obtained.
Stage #1: methanesulfonic acid; Diphenyliodonium-2-carboxylate In N,N-dimethyl-formamide at 23 - 70℃; for 1.5h;
Stage #2: 1-hydroxy-3-hydroxymethyladamantane In N,N-dimethyl-formamide at 70℃; for 1h;
Stage #3: C16H18F6O7S*C6H15N In N,N-dimethyl-formamide at 23℃; for 1h;
19 Example 19: Synthesis of salt represented by formula (I-796)
1.00 parts of the salt represented by the formula (I-438-a), 0.33 parts of methanesulfonic acid and 3 parts of dimethylformamide were mixed, stirred at 23 ° C. for 30 minutes, and then further at 70 ° C. for 1 hour. Stirred. To the obtained mixed solution, 0.80 part of the compound represented by the formula (I-786-b) was added, and the mixture was stirred at 70 ° C. for 1 hour and then cooled to 23 ° C. To the obtained mixed solution, 1.47 parts of a salt represented by the formula (I-100-d) was added, and after stirring at 23 ° C. for 1 hour, 30 parts of chloroform and 2 parts of a 5% aqueous oxalic acid solution and ions were added. 10 parts of exchanged water was added, and the mixture was stirred at 23 ° C. for 30 minutes, separated to remove the organic layer. After adding 10 parts of ion-exchanged water to the obtained organic layer and stirring at 23 ° C. for 30 minutes, the liquid was separated and the organic layer was taken out. This washing operation was repeated 3 times. The obtained organic layer is concentrated, and the concentrated mass is separated by a column (silica gel 60N (spherical, neutral) 100-210 μm; manufactured by Kanto Chemical Co., Inc., developing solvent: chloroform / methanol = 1/1). 0.18 parts of the salt represented by the formula (I-796) was obtained.
Stage #1: methanesulfonic acid; Diphenyliodonium-2-carboxylate In N,N-dimethyl-formamide at 23 - 70℃; for 1.5h;
Stage #2: 1-hydroxy-3-hydroxymethyladamantane In N,N-dimethyl-formamide at 70℃; for 1h;
Stage #3: C7H11N2(1+)*C24H29F2O8S(1-) In N,N-dimethyl-formamide at 23℃; for 1h;
18 Example 18: Synthesis of salt represented by formula (I-788)
1.00 parts of the salt represented by the formula (I-438-a), 0.33 parts of methanesulfonic acid and 3 parts of dimethylformamide were mixed, stirred at 23 ° C. for 30 minutes, and then further at 70 ° C. for 1 hour. Stirred. To the obtained mixed solution, 0.80 part of the compound represented by the formula (I-786-b) was added, and the mixture was stirred at 70 ° C. for 1 hour and then cooled to 23 ° C. To the obtained mixed solution, 1.66 parts of the salt represented by the formula (I-92-d) was added, and after stirring at 23 ° C. for 1 hour, 30 parts of chloroform and 2 parts of a 5% aqueous oxalic acid solution and ions were added. 10 parts of exchanged water was added, and the mixture was stirred at 23 ° C. for 30 minutes, separated, and the organic layer was taken out. After adding 10 parts of ion-exchanged water to the obtained organic layer and stirring at 23 ° C. for 30 minutes, the liquid was separated and the organic layer was taken out. This washing operation was repeated 3 times. The obtained organic layer is concentrated, and the concentrated mass is separated by a column (silica gel 60N (spherical, neutral) 100-210 μm; manufactured by Kanto Chemical Co., Inc., developing solvent: chloroform / methanol = 1/1). 0.25 parts of the salt represented by the formula (I-788) was obtained.
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