Name: 55896-93-0|Ethyl 2-(chlorosulfonyl)acetate|95%
Brand: Ambeed
SKU: A988376
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1
[ 89124-45-8 ]
[ 55896-93-0 ]

Yield	Reaction Conditions	Operation in experiment
80%	With trichlorophosphate	50.2 Preparation of (Ethoxycarbonyl)Methanesulfonyl Chloride Example 50-2 Preparation of (Ethoxycarbonyl)Methanesulfonyl Chloride A mixture of (ethoxycarbonyl)methanesulfonic acid (10 g, 60 mmol.) and POCl3 (45 mL) was heated at 125° C. for 5 h. The mixture was cooled and filtered, and excess POCl3 was removed to give crude (ethoxycarbonyl)methanesulfonyl chloride (8.1 g, 80%) used directly without purification.
	With thionyl chloride at 120℃;
	With trichlorophosphate at 125℃;

	With trichlorophosphate	1 2,4,6-Triisopropylphenyl(2,6-diisopropylphenylsulfamoyl)acetate Amixture of ethyl sulfoacetate (16.82 g, 100 mM) and POCl3 (30.67 g, 200 mM) was heated at 125° C. for 5 hours. The mixture was cooled and filtered, and excess POCl3 was removed to give ethyl chlorosulfonylacetate.
	With trichlorophosphate	1.A 2,4,6-Triisopropylphenyl N,N-dibenzylcarbamoylmethylsulfonate A mixture of ethyl sulfoacetate (16.82 g, 100 mM) and POCl3 (30.67 g, 200 mM) was heated at 125° C. for 5 hours. The mixture was cooled and filtered, and excess POCl3 was removed to give ethyl chlorosulfonylacetate.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2009/269305, 2009, A1
[2]Vieillefosse [Bulletin de la Societe Chimique de France, 1939, vol. <5>6, p. 35][Bulletin de la Societe Chimique de France, 1947, p. 353,354]
[3]Lee; Roark; Picard; Sliskovic; Roth; Stanfield; Hamelehle; Bousley; Krause [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 3, p. 289 - 294]
[4]Current Patent Assignee: PFIZER INC - US5491170, 1996, A
[5]Current Patent Assignee: PFIZER INC - US5510379, 1996, A

2
[ 55896-93-0 ]
[ 15950-17-1 ]
[ 61154-66-3 ]

Reference： [1]European Journal of Medicinal Chemistry,1976,vol. 11,p. 101 - 106

3
[ 55896-93-0 ]
[ 3360-79-0 ]
[ 61154-57-2 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In benzene

Reference： [1]Bianchi,M. et al. [European Journal of Medicinal Chemistry, 1976, vol. 11, p. 101 - 106]

4
[ 55896-93-0 ]
[ 25781-92-4 ]
[ 61154-60-7 ]

Reference： [1]European Journal of Medicinal Chemistry,1976,vol. 11,p. 101 - 106

5
[ 55896-93-0 ]
[ 55897-04-6 ]

Yield	Reaction Conditions	Operation in experiment
81%	Stage #1: ethyl 2-(chlorosulfonyl)acetate With 1,1,1,3,3,3-hexamethyl-disilazane In dichloromethane for 1h; Cooling with ice; Stage #2: With ethanol for 0.75h;	4.1.1 Preparation of ethyl 2-sulfamoylacetate (11) To a solution of ethyl 2-(chlorosulfonyl)acetate 14 [81,82] (1.87g, 10mmol) in dry DCM (8mL) under ice-cooling was slowly added hexamethyldisilazane (2.2mL, 10.5mmol). Mixture was stirred under cooling for 30min, and then 30min without bath. Solvent was removed in vacuo. The oily residue was cooled in ice bath, dissolved in ethanol (5mL), and stirred for 45min. Evaporation of solvent gave white solid, 1.35g (81%). 1H NMR (400MHz, CDCl3) δ 5.25 (br.s, 2H), 4.31 (q, J=7.2Hz, 2H), 4.14 (s, 2H), 1.35 (t, J=7.1Hz, 3H).
10%	With ammonia In tetrahydrofuran at 20℃; for 0.5h;	179.2 .S'te]l 2. To a 250 mL round-bottom flask was added ethyl2-(chlorosulfonyl)acetate 210b (3.2g, 17.15 mmol, 1.00 equiv.) and a 0.5M solution ofNH3 in tetrahydrofuran (80 mL). Theresulting solution was stirred at room temperature for 30 min and then concentrated undervacuurn. The residue -vvas treated with 5 mL of DCM :md purified by silica gel column10 chromatography eluting with dichloromethane/ethyl acetate (2: 1) to atiord ethyl 2-sulfamoylacetate 210c (300 mg, 10%) as a yellow oil.
	With ammonia In diethyl ether at 10℃; for 1h;

	With ammonia
	With 1,1,1,3,3,3-hexamethyl-disilazane In dichloromethane for 1h; 0 deg C to room temp.; Yield given;

Reference： [1]Dar'in, Dmitry; Kantin, Grigory; Kalinin, Stanislav; Sharonova, Tatiana; Bunev, Alexander; Ostapenko, Gennady I.; Nocentini, Alessio; Sharoyko, Vladimir; Supuran, Claudiu T.; Krasavin, Mikhail [European Journal of Medicinal Chemistry, 2021, vol. 222]
[2]Current Patent Assignee: ARDELYX, INC. - WO2018/39386, 2018, A1 Location in patent: Page/Page column 349; 350
[3]Le Berre,A. et al. [Bulletin de la Societe Chimique de France, 1975, p. 807 - 811]
[4]Gilmore; Lin [Journal of Organic Chemistry, 1978, vol. 43, # 23, p. 4535 - 4537]
[5]Britcher, Susan F.; Cochran, David W.; Phillips, Brian T.; Springer, James P.; Lumma, William C. [Journal of Organic Chemistry, 1983, vol. 48, # 6, p. 763 - 767]

6
[ 22128-42-3 ]
[ 55896-93-0 ]

Yield	Reaction Conditions	Operation in experiment
92%	With trichlorophosphate at 80℃; for 2h;
85%	With phosphorus pentachloride at 100℃; for 0.75h; Inert atmosphere;
65%	With phosphorus pentachloride at 20℃; for 0.333333h;	179.1 Step 1. To a 50 rnL rmmd-bottom Hask was added ethyl 2-[(sodiooxy)sulfonyl]acetate 21 Oa (5 g, 26.30 mmol, 1.00 equiv.) followed by phosphorous pentachloride (13.6 g, 65.31 mmol,2.50 equiv.). Tiw resulting rnixture was stirred at room temperature for 20 min. The mixturevas washed with toluene (40 mL x 3) and concentrated under vacuum to give of ethyl 2-(chlorosufonyl)acetate 210h (3.2 g, 65%) as a yellow oil

61%	With oxalyl dichloride In N,N-dimethyl-formamide; toluene at 100℃; for 3h; Inert atmosphere;
40%	With trichlorophosphate at 80℃; for 2h;
	With phosphorus pentachloride In benzene
	With phosphorus pentaoxide In dichloromethane	51.A Step A Step A Preparation of ethyl 2-chlorosulfonylacetate Sodium 2-ethoxy-2-oxo-1-ethanesulfonate (3.52 g, 18.53 mmol) and phosphorus pentoxide (4.6 g, 22 mmol) were placed in a round bottom flask with a condenser and stirred magnetically for 1 hr. A liquid resulted which was stirred 1 hr at rt, then 1 hr at 100° C. while a copious white precipitate of NaCl formed. The reaction was concentrated to dryness, dissolved in CH2Cl2, filtered through a silica plug, and concentrated to yield the title compound as a light yellow oil.
	With phosphorus pentachloride In neat (no solvent) for 2h; Reflux;	Ethyl-2-[N-(4-fluorophenyl) sulfamoyl acetate (11a) Sodium -2-ethoxy-2-oxoethanesulfonate (40 g, 0.21 mol) & Phosphorous pentachloride (45.5 g, 0.22 mol) were mixed in a RB fitted with a reflux condenser. The reaction mixture was vigorously stirred magnetic stirrer for 15 min. The reaction mixture became exothermic & started refluxing. The reaction mixture was allowed to reflux for 2 h with external heating & cooled to RT. The reaction mixture was stripped off the POCl3 produced in the reaction mixture & added toluene and filtered. The filtrate obtained was added to a cooled mixture of Triethyl amine (42.6g, 0.42 mol) & 4-Fluoroaniline (27.5g, 0.23 mol) in DCM (200 mL). The reaction mixture was allowed to stir for 16 h at RT & added water (200 mL)and extracted with DCM. The DCM layer was washed with 1N HCl, followed by sat.aq bicarbonate solution, brine & dried over sodium sulfate. The DCM layer was concentrated under reduced pressure to get dark residue. Yield =65 %. 1HNMR (400 MHz, Chloroform-d6) δ 7.36 - 7.30 (m, 2H), 7.10 - 7.06 (m, 2H), 4.3 (q, 2H), 3.9 (s, 2H), 1.3 (t, 3H).LCMS (m+1) 261.8
	With phosphorus pentachloride at 100℃; for 16.5h;	2 Step 2: ethyl 2- (chlorosulfonyl) acetate Sodium 2-ethoxy-2-oxoethanesulfonate (300 g, 1.58 mol) and PCl5(360 g, 1.73 mol) were added to a 1 L round-bottomed flask. The resultant mixture was stirred for 30 minutes during which time there was an exotherm and the solids liquified. The resulting mixture was stirred and heated at 100 for 16 hours, then cooled to room-temperature and concentrating to dryness under reduced pressure. The residue was triturated with toluene (500 mL) , filtered, and the filtrate concentrated to dryness under reduced pressure to afford the title compound (180 g, crude) , which was used in the next step without purification.
67 g	With oxalyl dichloride In dichloromethane at 20℃; for 16h;

Reference： [1]Liu, Yajing; Liu, Zijian; Shi, Jiyue; Chen, Huimin; Mi, Bin; Li, Peng; Gong, Ping [Molecules, 2013, vol. 18, # 3, p. 2864 - 2877]
[2]Reddy, M. V. Ramana; Mallireddigari, Muralidhar R.; Pallela, Venkat R.; Cosenza, Stephen C.; Billa, Vinay K.; Akula, Balaiah; Subbaiah, D. R. C. Venkata; Bharathi, E. Vijaya; Padgaonkar, Amol; Lv, Hua; Gallo, James M.; Reddy, E. Premkumar [Journal of Medicinal Chemistry, 2013, vol. 56, # 13, p. 5562 - 5586]
[3]Current Patent Assignee: ARDELYX, INC. - WO2018/39386, 2018, A1 Location in patent: Page/Page column 349; 350
[4]Cao, Lidong; Weidner, Karin; Renaud, Philippe [Advanced Synthesis and Catalysis, 2011, vol. 353, # 18, p. 3467 - 3472]
[5]Fang, Wan-Yin; Wang, Shi-Meng; Zhang, Zai-Wei; Qin, Hua-Li [Organic Letters, 2020, vol. 22, # 22, p. 8904 - 8909]
[6]Oliver; DeMilo [Synthesis, 1975, vol. No. 5, p. 321 - 322]
[7]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US2003/55244, 2003, A1
[8]Chandrasekharappa, Arun P.; Badiger, Sangamesh E.; Dubey, Pramod K.; Panigrahi, Sunil K.; Manukonda, Sekhar Reddy V.V.V. [Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 9, p. 2579 - 2584]
[9]Current Patent Assignee: HUTCHISON CHINA MEDITECH LTD. - WO2016/119707, 2016, A1 Location in patent: Paragraph 157
[10]Górski, Bartosz; Basiak, Dariusz; Talko, Alicja; Basak, Tymoteusz; Mazurek, Tomasz; Barbasiewicz, Michał [European Journal of Organic Chemistry, 2018, vol. 2018, # 15, p. 1774 - 1784]

7
[ 55896-93-0 ]
[ 75-64-9 ]
[ 67541-92-8 ]

Yield	Reaction Conditions	Operation in experiment
43%	In tetrahydrofuran	50.3 Preparation of ethyl-2-(N-tert-butylsulfamoyl)acetate Example 50-3 Preparation of ethyl-2-(N-tert-butylsulfamoyl)acetate tert-Butylamine (7.9 mL, 75 mmol.) was dissolved in 50 mL of THF. The solution was cooled to -20° C. and (ethoxycarbonyl)methanesulfonyl chloride dissolved in 10 mL of THF was added slowly. The reaction mixture was allowed to warm to room temperature and stirred for 24 h. The mixture was filtered, and the filtrate concentrated in vacuo. The residue was purified by column chromatography (PE/EtOAc; 2:1) to afford ethyl-2-(N-tert-butylsulfamoyl)acetate (4.1 g, 43%).
	In dichloromethane
24 g	With triethylamine In dichloromethane at 0℃; for 16.5h;	2-(N-(tert-butyl)sulfamoyl)acetic acid (22) Sodium -2-ethoxy-2-oxoethanesulfonate (30 g, 0.157 mol) & Phosphorous pentachloride (3809 g, 0.19 mol) were mixed in a RB fixed with a reflux condenser. The reaction mixture was allowed to stir for 10 - 15 min. The reaction mixture became exothermic & started refluxing. The reaction mixture was allowed to reflux for 2 h with external heating & cooled to RT. The reaction mixture was stripped off the POCl3 produced in the reaction mixture & added DCM (150 mL). The reaction mixture was added to a stirring mixture of Triethyl amine (31.89 g, 0.314 mol) & tert-butyl amine (12.6 g, 0.172 mol) in DCM (100 mL) at 0°C for 30 min. The reaction mixture was allowed to stir for 16 h & added water and extracted with DCM. The DCM layer was washed with 1N HCl , washed with sat.aq bicarbonate solution, brine & dried over sodium sulfate. The DCM layer was concentrated under reduced pressure to get dark residue.Residue obtained (24 g) from the above reaction was dissolved in tetrahydrouran (100 ML) and to that added aqueous KOH solution (12 g in 200 mL of water) slowly at 0°C and allowed the reaction mixture to stir at RT for 6h. The reaction mixture was stripped off the THF and acidified with 3N HCl to pH ~ 2. The aqueous layer was extracted with ethyl acetate, ethyl acetate layer washed with brine, dried over sodium sulphate and concentrated. Yield =60%. 1HNMR (400 MHz, Chloroform-d6) δ 5.3 (brs, 1H), 4.12 (s, 2H), 1.4 (s, 9H).

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2009/269305, 2009, A1
[2]Gilmore; Lin [Journal of Organic Chemistry, 1978, vol. 43, # 23, p. 4535 - 4537]
[3]Chandrasekharappa, Arun P.; Badiger, Sangamesh E.; Dubey, Pramod K.; Panigrahi, Sunil K.; Manukonda, Sekhar Reddy V.V.V. [Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 9, p. 2579 - 2584]

8
[ 17284-97-8 ]
[ 55896-93-0 ]
[ 75680-93-2 ]
[ 76195-97-6 ]
[ 69579-06-2 ]

Yield	Reaction Conditions	Operation in experiment
1: 500 mg 2: 30% 3: 150 mg	With triethylamine In dichloromethane 1.) 10 h., room temp.; 2.) reflux, 2 h.;
1: 500 mg 2: 150 mg 3: 30%	With triethylamine In dichloromethane 1.) 10 h., room temp.; 2.) reflux 2 h.;

Reference： [1]Kosary, J.; Sohar, P. [Acta Chimica Academiae Scientiarum Hungaricae, 1980, vol. 103, # 4, p. 405 - 414]
[2]Kosary, J.; Sohar, P. [Acta Chimica Academiae Scientiarum Hungaricae, 1980, vol. 103, # 4, p. 405 - 414]

9
[ 58743-30-9 ]
[ 55896-93-0 ]
[ 58742-77-1 ]

Reference： [1]Archiv der Pharmazie,1985,vol. 318,p. 304 - 311

10
[ 55896-93-0 ]
[ 106-49-0 ]
[ 78374-64-8 ]

Yield	Reaction Conditions	Operation in experiment
72%	With triethylamine In tetrahydrofuran at 0 - 20℃; for 1h; Inert atmosphere;	6.2 General methods for preparation of linear sulfonamide 3a-c General procedure: Sulfonyl chloride 1 (33mmol) in THF (10mL) was added dropwise to a solution of aromatic amine 2 (33mmol) and triethylamine (4.4mL, 35mmol) in 100mL THF at 0°C. Upon completion of the addition, the reaction mixture was stirred at room temperature for 1h before concentrated in vacuo. The residue was dissolved in EtOAc (100mL), washed with saturated brine (3×20mL), dried over Na2SO4, and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel to give compounds 3a-c.
60%	With triethylamine In benzene

Reference： [1]Zhang, Wei; Ai, Jing; Shi, Dakuo; Peng, Xia; Ji, Yinchun; Liu, Jian; Geng, Meiyu; Li, Yingxia [European Journal of Medicinal Chemistry, 2014, vol. 80, p. 254 - 266]
[2]Shridhar, D. R.; Sastry, C. V. Reddy; Lal, K. B.; Marwah, A. K.; Reddi, G. S.; et al. [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1981, vol. 20, # 3, p. 234 - 237]

11
[ 55896-93-0 ]
[ 62-53-3 ]
[ 56146-84-0 ]

Yield	Reaction Conditions	Operation in experiment
80%	With triethylamine In dichloromethane at 20℃; for 3h; Inert atmosphere;
65%	With triethylamine In tetrahydrofuran at 0 - 20℃; for 1h; Inert atmosphere;	6.2 General methods for preparation of linear sulfonamide 3a-c General procedure: Sulfonyl chloride 1 (33mmol) in THF (10mL) was added dropwise to a solution of aromatic amine 2 (33mmol) and triethylamine (4.4mL, 35mmol) in 100mL THF at 0°C. Upon completion of the addition, the reaction mixture was stirred at room temperature for 1h before concentrated in vacuo. The residue was dissolved in EtOAc (100mL), washed with saturated brine (3×20mL), dried over Na2SO4, and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel to give compounds 3a-c.
60%	With triethylamine In benzene

52%
	With triethylamine In toluene at -5 - 20℃;

Reference： [1]Reddy, M. V. Ramana; Mallireddigari, Muralidhar R.; Pallela, Venkat R.; Cosenza, Stephen C.; Billa, Vinay K.; Akula, Balaiah; Subbaiah, D. R. C. Venkata; Bharathi, E. Vijaya; Padgaonkar, Amol; Lv, Hua; Gallo, James M.; Reddy, E. Premkumar [Journal of Medicinal Chemistry, 2013, vol. 56, # 13, p. 5562 - 5586]
[2]Zhang, Wei; Ai, Jing; Shi, Dakuo; Peng, Xia; Ji, Yinchun; Liu, Jian; Geng, Meiyu; Li, Yingxia [European Journal of Medicinal Chemistry, 2014, vol. 80, p. 254 - 266]
[3]Shridhar, D. R.; Sastry, C. V. Reddy; Lal, K. B.; Marwah, A. K.; Reddi, G. S.; et al. [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1981, vol. 20, # 3, p. 234 - 237]
[4]Baltas, Michel; Cazaux, Louis; Blic, Arnold de; Gorrichon, Liliane; Tisnes, Pierre; Touati, Abdelkader [Bulletin de la Societe Chimique de France, 1988, # 1, p. 79 - 87]
[5]Liu, Yajing; Liu, Zijian; Shi, Jiyue; Chen, Huimin; Mi, Bin; Li, Peng; Gong, Ping [Molecules, 2013, vol. 18, # 3, p. 2864 - 2877]

12
[ 626-89-1 ]
[ 55896-93-0 ]
C₁₀H₂₀O₅S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With 1H-imidazole In tetrahydrofuran

Reference： [1]Wolckenhauer, Scott A.; Devlin, A. Sloan; Du Bois [Organic Letters, 2007, vol. 9, # 21, p. 4363 - 4366]

13
[ 55896-93-0 ]
[ 530-91-6 ]
C₁₄H₁₈O₅S [ No CAS ]

Reference： [1]Organic Letters,2007,vol. 9,p. 4363 - 4366

14
3-Chloro-4-(1-methyl-piperidin-4-yloxy)-phenylamine [ No CAS ]
[ 55896-93-0 ]
[ 470476-92-7 ]

Yield	Reaction Conditions	Operation in experiment
81%	With pyridine In dichloromethane at 20℃; for 5h;
81%	With pyridine In dichloromethane at 0 - 20℃; for 5h;	6 Reference example 6; Ethyl N-[3-chloro-4-(1-methylpiperidin-4-yloxy)phenyl]sulfamoylacetate To a solution of 3-chloro-4-(1-methylpiperidin-4-yloxy)aniline (6.95 g) obtained in reference example 5 in dichloromethane (150 ml) were successively added dropwise ethyl chlorosulfonylacetate (3.88 ml) and pyridine (4.67 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature for 5 hours. After stirring, to the reaction mixture was added water, and the resulting mixture was extracted with ethyl acetate three times. The extract was dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of dichloromethane and methanol (4:1 ~ 1:1) as the eluent to afford the title compound (9.12 g, yield: 81 %) as a brown amorphous solid. 1H NMR (500MHz, CDCl3) δ ppm : 1.34 (3H, t, J=7.0), 1.90-2.00 (2H, m), 2.00-2.10 (2H, m), 2.37 (3H, s), 2.40-2.50 (2H, m), 2.70-2.80 (2H, m), 3.92 (2H, s), 4.30 (2H, q, J=7.0), 4.41 (1H, m), 6.93 (1H, d, J=9.0), 7.21 (1H, dd, J=9.0, 2.5), 7.40 (1H, d, J=2.5).

Reference： [1]Location in patent: experimental part Noguchi, Tetsuji; Tanaka, Naoki; Nishimata, Toyoki; Goto, Riki; Hayakawa, Miho; Sugidachi, Atsuhiro; Ogawa, Taketoshi; Niitsu, Yoichi; Asai, Fumitoshi; Ishizuka, Tomoko; Fujimoto, Koichi [Chemical and Pharmaceutical Bulletin, 2009, vol. 57, # 1, p. 22 - 33]
[2]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 133

15
[ 55896-93-0 ]
[ 876-30-2 ]
[ 337522-37-9 ]

Yield	Reaction Conditions	Operation in experiment
67%	With pyridine In dichloromethane at 0 - 20℃;	96 Reference example 96; ethyl N-(4-methoxymethoxyphenyl)sulfamoylacetate To a solution of 4-methoxymethoxyaniline (20.9 g) in dichloromethane (400 ml) were successively added dropwise ethyl chlorosulfonylacetate (18.0 ml) and pyridine (33 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature overnight.. After stirring, to the reaction mixture was added water, and the resulting mixture was extracted with ethyl acetate.. The extract was washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and evaporated in vacuo.. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of hexane and ethyl acetate (3:2) as the eluent to afford the title compound (28.0 g, yield: 67 %) as a brown oil. 1H NMR (500MHz, CDCl3) δ ppm: 1.33 (3H, t, J=7.0), 3.48 (3H, s), 3.90 (2H, s), 4.29 (2H, q, J=7.0), 5.16 (2H, s), 7.03 (2H, d, J=9.0), 7.28 (2H, d, J=9.0).
	With pyridine In dichloromethane at 0℃; for 2.5h;

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 157
[2]Location in patent: experimental part Noguchi, Tetsuji; Tanaka, Naoki; Nishimata, Toyoki; Goto, Riki; Hayakawa, Miho; Sugidachi, Atsuhiro; Ogawa, Taketoshi; Asai, Fumitoshi; Fujimoto, Koichi [Chemical and Pharmaceutical Bulletin, 2008, vol. 56, # 6, p. 758 - 770]

16
[ 138227-69-7 ]
[ 55896-93-0 ]
[ 337519-92-3 ]

Yield	Reaction Conditions	Operation in experiment
76%	With pyridine In dichloromethane at 0 - 20℃; for 5h;	111 Reference example 111; Ethyl N-[4-(1-t-butoxycarbonylpiperidin-4-yloxy)-3-methylphenyl]sulfamoylacetate To a solution of 4-(1-t-butoxycarbonylpiperidin-4-yloxy)-3-methylaniline (1.63 g) obtained in reference example 110 in dichloromethane (30 ml) were successively added dropwise ethyl chlorosulfonylacetate (0.86 ml) and pyridine (0.81 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature for 5 hours and then evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of hexane and ethyl acetate (3:2) as the eluent to afford the title compound (1.84 g, yield: 76 %) as a pale brown amorphous solid. 1H NMR (500MHz, CDCl3) δ ppm : 1.34 (3H, t, J=7.0), 1.47 (9H, s), 1.78 (2H, m), 1.89 (2H, m), 2.22 (3H, s), 3.43 (2H, m), 3.62 (2H, m), 3.90 (2H, s), 4.29 (2H, q, J=7.0), 4.48 (1H, m), 6.79 (1H, d, J=8.0), 7.12 (2H, m).
	With pyridine In dichloromethane

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 160
[2]Location in patent: experimental part Noguchi, Tetsuji; Tanaka, Naoki; Nishimata, Toyoki; Goto, Riki; Hayakawa, Miho; Sugidachi, Atsuhiro; Ogawa, Taketoshi; Asai, Fumitoshi; Fujimoto, Koichi [Chemical and Pharmaceutical Bulletin, 2008, vol. 56, # 6, p. 758 - 770]

17
[ 55896-93-0 ]
[ 325457-62-3 ]
[ 337519-90-1 ]

Yield	Reaction Conditions	Operation in experiment
73%	With pyridine In dichloromethane at 0 - 20℃; for 3h;	121 Reference example 121;Ethyl N-[4-(1-t-butoxycarbonylpiperidin-4-yloxy)-3-trifluoromethylphenyl]sulfamoylacetate To a solution of 4-(1-t-butoxycarbonylpiperidin-4-yloxy)-3-trifluoromethylaniline (1.69 g) obtained in reference example 120 in dichloromethane (20 ml) were successively added dropwise ethyl chlorosulfonylacetate (0.76 ml) and pyridine (0.49 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature for 3 hours and then evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of hexane and ethyl acetate (3:2) as the eluent to afford the title compound (1.74 g, yield: 73 %) as a pale red oil. 1H NMR (500MHz, CDCl3) δ ppm : 1.34 (3H, t, J=7.0), 1.48 (9H, s), 1.83-1.94 (4H, m), 3.48-3.60 (4H, m), 3.91 (2H, s), 4.31 (2H, q, J=7.0), 4.65 (1H, m), 6.99 (1H, d, J=9.0), 7.52 (1H, dd, J=9.0, 2.5), 7.56 (1H, d, J=2.5).
	With pyridine In dichloromethane

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 163
[2]Location in patent: experimental part Noguchi, Tetsuji; Tanaka, Naoki; Nishimata, Toyoki; Goto, Riki; Hayakawa, Miho; Sugidachi, Atsuhiro; Ogawa, Taketoshi; Asai, Fumitoshi; Fujimoto, Koichi [Chemical and Pharmaceutical Bulletin, 2008, vol. 56, # 6, p. 758 - 770]

18
4-(N-methylpiperidin-4-yl)oxy-3-trifluoromethylbenzenamine [ No CAS ]
[ 55896-93-0 ]
[ 470477-78-2 ]

Yield	Reaction Conditions	Operation in experiment
100%	With pyridine In dichloromethane at 0 - 20℃; for 1h;	103 Reference example 103; Ethyl N-[4-(1-methylpiperidin-4-yloxy)-3-trifluoromethylphenyl]sulfamoylacetate To a solution of 4-(1-methylpiperidin-4-yloxy)-3-trifluoromethylaniline (1.55 g) obtained in reference example 102 in dichloromethane (30 ml) were successively added dropwise ethyl chlorosulfonylacetate (0.76 ml) and pyridine (0.91 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature for 1 hour. After stirring, to the reaction mixture was added water, and the resulting mixture was extracted with ethyl acetate three times. The extract was washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of dichloromethane and methanol (10:1 ~ 5:1) as the eluent to afford the title compound (2.39 g, quantitative yield) as a pale brown amorphous solid. 1H NMR (400MHz, CDCl3) δ ppm : 1.34 (3H, t, J=7.0), 2.00-2.15 (2H, m), 2.35-2.50 (2H, m), 2.62 (3H, s), 2.80-3.15 (4H, m), 3.92 (2H, s), 4.30 (2H, q, J=7.0), 4.72 (1H, m), 6.98 (1H, d, J=9.0), 7.55 (1H, dd, J=9.0, 2.5), 7.62 (1H, d, J=2.5).

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 158-159

19
[ 337519-87-6 ]
[ 55896-93-0 ]
[ 337519-88-7 ]

Yield	Reaction Conditions	Operation in experiment
54%	With pyridine In dichloromethane at 0 - 20℃; for 5h;	69 Reference example 69; Ethyl N-[4-(1-t-butoxycarbonylpiperidin-4-yloxy)-3-chlorophenyl]sulfamoylacetate To a solution of 4-(1-t-butoxycarbonylpiperidin-4-yloxy)-3-chloroaniline (1.50 g) obtained in reference example 68 in dichloromethane (20 ml) were successively added dropwise ethyl chlorosulfonylacetate (0.74 ml) and pyridine (0.56 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature for 5 hours and then evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of hexane and ethyl acetate (3:2) as the eluent to afford the title compound (1.19 g, yield: 54 %) as a pale red oil. 1H NMR (500MHz, CDCl3) δ ppm : 1.34 (3H, t, J=7.0), 1.47 (9H, s), 1.79-1.92 (4H, m), 3.46 (2H, m), 3.64 (2H, m), 3.92 (2H, s), 4.30 (2H, q, J=7.0), 4.52 (1H, m), 6.94 (2H, d, J=9.0), 7.22 (1H, dd, J=9.0, 2.5), 7.40 (1H, d, J=2.5).
	With pyridine In dichloromethane

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 149
[2]Location in patent: experimental part Noguchi, Tetsuji; Tanaka, Naoki; Nishimata, Toyoki; Goto, Riki; Hayakawa, Miho; Sugidachi, Atsuhiro; Ogawa, Taketoshi; Asai, Fumitoshi; Fujimoto, Koichi [Chemical and Pharmaceutical Bulletin, 2008, vol. 56, # 6, p. 758 - 770]

20
[ 337520-26-0 ]
[ 55896-93-0 ]
[ 337520-27-1 ]

Yield	Reaction Conditions	Operation in experiment
53%	With pyridine In dichloromethane at 0 - 20℃; for 6h;	118 Reference example 118; Ethyl N-[4-(1-t-butoxycarbonylpiperidin-4-yloxy)-3-carbamoylphenyl]sulfamoylacetate To a solution of 4-(1-t-butoxycarbonylpiperidin-4-yloxy)-3-carbamoylaniline (4.8 g) obtained in reference example 117 in dichloromethane (80 ml) were successively added dropwise ethyl chlorosulfonylacetate (2.5 ml) and pyridine (2.3 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature for 6 hours and then evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of dichloromethane and methanol (19:1) as the eluent. The orange-colored solid obtained was collected by filtration using diethyl ether to afford the title compound (3.7 g, yield: 53 %) as a pale yellow solid. 1H NMR (500MHz, CDCl3) δ ppm : 1.32 (3H, t, J=7.0), 1.47 (9H, s), 1.70-1.85 (2H, m), 2.00-2.15 (2H, m), 3.27 (2H, m), 3.75-3.85 (2H, m), 3.94 (2H, s), 4.28 (2H, q, J=7.0), 4.65 (1H, m), 7.02 (1H, d, J=9.0), 7.59 (1H, dd, J=9.0, 3.0), 8.12 (1H, d, J=3.0).
	With pyridine In dichloromethane

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 162
[2]Location in patent: experimental part Noguchi, Tetsuji; Tanaka, Naoki; Nishimata, Toyoki; Goto, Riki; Hayakawa, Miho; Sugidachi, Atsuhiro; Ogawa, Taketoshi; Asai, Fumitoshi; Fujimoto, Koichi [Chemical and Pharmaceutical Bulletin, 2008, vol. 56, # 6, p. 758 - 770]

21
[ 470476-96-1 ]
[ 55896-93-0 ]
[ 470477-24-8 ]

Yield	Reaction Conditions	Operation in experiment
76%	With pyridine In dichloromethane at 0 - 20℃; for 3.5h;	38 Reference example 38; Ethyl N-[4-(1-acetylpiperidin-4-yloxy)-3-chlorophenyl]sulfamoylacetate To a solution of 4-(1-acetylpiperidin-4-yloxy)-3-chloroaniline (650 mg) obtained in reference example 10 in dichloromethane (20 ml) were successively added dropwise ethyl chlorosulfonylacetate (0.33 ml) and pyridine (0.39 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature for 3.5 hours and then evaporated in vacuo. The residue obtained was diluted with ethyl acetate, and the organic layer was washed successively with a saturated aqueous sodium hydrogencarbonate solution and a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column (eluent: ethyl acetate only ~ a mixed solvent of ethyl acetate and methanol (10:1)) to afford the title compound (773 mg, yield: 76 %) as an orange-colored oil. 1H NMR (400MHz, CDCl3) δ ppm : 1.34 (3H, t, J=7.0), 1.82-1.98 (4H, m), 2.13 (3H, s), 3.47 (1H, m), 3.63 (1H, m), 3.72 (1H, m), 3.84 (1H, m), 3.92 (2H, s), 4.30 (2H, q, J=7.0), 4.60 (1H, m), 6.94 (1H, d, J=9.0), 7.23 (1H, dd, J=9.0, 2.5), 7.41 (1H, d, J=2.5).

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 141

22
[ 470476-97-2 ]
[ 55896-93-0 ]
[ 470476-98-3 ]

Yield	Reaction Conditions	Operation in experiment
82%	With pyridine In dichloromethane at 0 - 20℃; for 4h;	12 Reference example 12; Ethyl N-[3-chloro-4-(1-ethylpiperidin-4-yloxy)phenyl]sulfamoylacetate To a solution of 3-chloro-4-(1-ethylpiperidin-4-yloxy)aniline (853 mg) obtained in reference example 11 in dichloromethane (20 ml) were successively added dropwise ethyl chlorosulfonylacetate (0.45 ml) and pyridine (0.54 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature for 4 hours. After stirring, to the reaction mixture was added water, and the resulting mixture was extracted with ethyl acetate twice. The extract was dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of dichloromethane and methanol (3:1 ~ 1:1) as the eluent to afford the title compound (1113 mg, yield: 82 %) as a yellowish brown amorphous solid. 1H NMR (400MHz, CDCl3) δ ppm : 1.15 (3H, t, J=7.0), 1.34 (3H, t, J=7.0), 1.87-2.00 (2H, m), 2.00-2.13 (2H, m), 2.40-2.60 (4H, m), 2.70-2.83 (2H, m), 3.92 (2H, s), 4.30 (2H, q, J=7.0), 4.43 (1H, m), 6.93 (1H, d, J=9.0), 7.21 (1H, dd, J=9.0, 2.5), 7.40 (1H, d, J=2.5).
	With pyridine In dichloromethane at 20℃;

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 134
[2]Location in patent: experimental part Noguchi, Tetsuji; Tanaka, Naoki; Nishimata, Toyoki; Goto, Riki; Hayakawa, Miho; Sugidachi, Atsuhiro; Ogawa, Taketoshi; Niitsu, Yoichi; Asai, Fumitoshi; Ishizuka, Tomoko; Fujimoto, Koichi [Chemical and Pharmaceutical Bulletin, 2009, vol. 57, # 1, p. 22 - 33]

23
[ 470477-01-1 ]
[ 55896-93-0 ]
[ 470477-02-2 ]

Yield	Reaction Conditions	Operation in experiment
71%	With pyridine In dichloromethane at 0 - 20℃; for 4h;	16 Reference example 16; Ethyl N-[3-chloro-4-(1-isopropylpiperidin-4-yloxy)phenyl]sulfamoylacetate To a solution of 3-chloro-4-(1-isopropylpiperidin-4-yloxy)aniline (985 mg) obtained in reference example 15 in dichloromethane (20 ml) were successively added dropwise ethyl chlorosulfonylacetate (0.49 ml) and pyridine (0.59 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature for 4 hours. After stirring, to the reaction mixture was added water, and the resulting mixture was extracted with ethyl acetate twice. The organic layer was dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of dichloromethane and methanol (10:1 ~ 3:1) as the eluent to afford the title compound (1094 mg, yield: 71 %) as an orange-colored amorphous solid. 1H NMR (400MHz, CDCl3) δ ppm : 1.10 (6H, d, J=6.5), 1.33 (3H, t, J=7.0), 1.84-1.98 (2H, m), 1.98-2.12 (2H, m), 2.50 (2H, m), 2.76-2.90 (3H, m), 3.92 (2H, s), 4.29 (2H, q, J=7.0), 4.39 (1H, m), 6.93 (1H, d, J=9.0), 7.20 (1H, dd, J=9.0, 2.5), 7.39 (1H, d, J=2.5).
	With pyridine In dichloromethane at 20℃;

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 135-136
[2]Location in patent: experimental part Noguchi, Tetsuji; Tanaka, Naoki; Nishimata, Toyoki; Goto, Riki; Hayakawa, Miho; Sugidachi, Atsuhiro; Ogawa, Taketoshi; Niitsu, Yoichi; Asai, Fumitoshi; Ishizuka, Tomoko; Fujimoto, Koichi [Chemical and Pharmaceutical Bulletin, 2009, vol. 57, # 1, p. 22 - 33]

24
[ 470477-05-5 ]
[ 55896-93-0 ]
[ 470477-06-6 ]

Yield	Reaction Conditions	Operation in experiment
84%	With pyridine In dichloromethane at 0 - 20℃;	20 Reference example 20; Ethyl N-[4-(1-butylpiperidin-4-yloxy)-3-chlorophenyl]sulfamoylacetate To a solution of 4-(1-butylpiperidin-4-yloxy)-3-chloroaniline (1.09 g) obtained in reference example 19 in dichloromethane (20 ml) were successively added dropwise ethyl chlorosulfonylacetate (0.52 ml) and pyridine (0.62 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature overnight and then evaporated in vacuo. The residue obtained was diluted with ethyl acetate, and the organic layer was washed with an aqueous sodium hydrogencarbonate solution, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of dichloromethane and methanol (20:1 ~ 9:1) as the eluent to afford the title compound (1.41 g, yield: 84 %) as a brown amorphous solid. 1H NMR (500MHz, CDCl3) δ ppm : 0.93 (3H, t, J=7.5), 1.34 (3H, t, J=7.0), 1.28-1.38 (2H, m), 1.54 (2H, m), 1.86-1.99 (2H, m), 2.02-2.15 (2H, m), 2.40-2.60 (4H, m), 2.79 (2H, m), 3.92 (2H, s), 4.30 (2H, q, J=7.0), 4.41 (1H, m), 6.93 (1H, d, J=9.0), 7 .21 (1H, dd, J=9.0, 2.5), 7.40 (1H, d, J=2.5).
	With pyridine In dichloromethane at 20℃;

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 136-137
[2]Location in patent: experimental part Noguchi, Tetsuji; Tanaka, Naoki; Nishimata, Toyoki; Goto, Riki; Hayakawa, Miho; Sugidachi, Atsuhiro; Ogawa, Taketoshi; Niitsu, Yoichi; Asai, Fumitoshi; Ishizuka, Tomoko; Fujimoto, Koichi [Chemical and Pharmaceutical Bulletin, 2009, vol. 57, # 1, p. 22 - 33]

25
[ 470477-09-9 ]
[ 55896-93-0 ]
[ 470477-10-2 ]

Yield	Reaction Conditions	Operation in experiment
89%	With pyridine In dichloromethane at 0 - 20℃; for 2.5h;	24 Reference example 24; Ethyl N-[4-(1-benzylpiperidin-4-yloxy)-3-chlorophenyl]sulfamoylacetate To a solution of 4-(1-benzylpiperidin-4-yloxy)-3-chloroaniline (780 mg) obtained in reference example 23 in dichloromethane (20 ml) were successively added dropwise ethyl chlorosulfonylacetate (0.35 ml) and pyridine (0.40 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature for 2.5 hours and then evaporated in vacuo. The residue obtained was diluted with ethyl acetate, and the organic layer was washed successively with an aqueous sodium hydrogencarbonate solution and a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of ethyl acetate and methanol (25:2) as the eluent to afford the title compound (1018 mg, yield: 89 %) as a yellowish brown amorphous solid. 1H NMR (400MHz, CDCl3) δ ppm : 1.33 (3H, t, J=7.0), 1.84-1.93 (2H, m), 1.93-2.02 (2H, m), 2.36 (2H, m), 2.73 (2H, m), 3.54 (2H, s), 3.91 (2H, s), 4.29 (2H, q, J=7.0), 4.37 (1H, m), 6.92 (1H, d, J=9.0), 7.19 (1H, dd, J=9.0, 2.5), 7.27 (1H, m), 7.29-7.37 (4H, m), 7.38 (1H, d, J=2.5).
	With pyridine In dichloromethane at 20℃;

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 137-138
[2]Location in patent: experimental part Noguchi, Tetsuji; Tanaka, Naoki; Nishimata, Toyoki; Goto, Riki; Hayakawa, Miho; Sugidachi, Atsuhiro; Ogawa, Taketoshi; Niitsu, Yoichi; Asai, Fumitoshi; Ishizuka, Tomoko; Fujimoto, Koichi [Chemical and Pharmaceutical Bulletin, 2009, vol. 57, # 1, p. 22 - 33]

26
[ 470477-13-5 ]
[ 55896-93-0 ]
[ 470477-14-6 ]

Yield	Reaction Conditions	Operation in experiment
89%	With pyridine In dichloromethane at 0 - 20℃; for 3h;	28 Reference example 28; Ethyl N-[3-chloro-4-(1-phenethylpiperidin-4-yloxy)phenyl]sulfamoylacetate To a solution of 3-chloro-4-(1-phenethylpiperidin-4-yloxy)aniline (720 mg) obtained in reference example 27 in dichloromethane (20 ml) were successively added dropwise ethyl chlorosulfonylacetate (0.31 ml) and pyridine (0.35 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature for 3 hours and then evaporated in vacuo. The residue obtained was diluted with ethyl acetate, and the organic layer was washed successively with an aqueous sodium hydrogencarbonate solution and a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of ethyl acetate and methanol (25:2) as the eluent to afford the title compound (936 mg, yield: 89 %) as a yellow amorphous solid. 1H NMR (500MHz, CDCl3) δ ppm : 1.34 (3H, t, J=7.0), 1.88-1.98 (2H, m), 1.98-2.08 (2H, m), 2.48 (2H, m), 2.60-2.70 (2H, m), 2.76-2.89 (4H, m), 3.92 (2H, s), 4.30 (2H, q, J=7.0), 4.41 (1H, m), 6.93 (1H, d, J=9.0), 7.18-7.24 (4H, m), 7. 24-7.33 (2H, m), 7.39 (1H, d, J=2.5) .
	With pyridine In dichloromethane at 20℃;

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 138-139
[2]Location in patent: experimental part Noguchi, Tetsuji; Tanaka, Naoki; Nishimata, Toyoki; Goto, Riki; Hayakawa, Miho; Sugidachi, Atsuhiro; Ogawa, Taketoshi; Niitsu, Yoichi; Asai, Fumitoshi; Ishizuka, Tomoko; Fujimoto, Koichi [Chemical and Pharmaceutical Bulletin, 2009, vol. 57, # 1, p. 22 - 33]

27
[ 470477-17-9 ]
[ 55896-93-0 ]
[ 470477-18-0 ]

Yield	Reaction Conditions	Operation in experiment
88%	With pyridine In dichloromethane at 0 - 20℃; for 2h;	32 Reference example 32; Ethyl N-[3-chloro-4-(1-phenylpiperidin-4-yloxy)phenyl]sulfamoylacetate To a solution of 3-chloro-4-(1-phenylpiperidin-4-yloxy)aniline (1.69 g) obtained in reference example 31 in dichloromethane (25 ml) were successively added dropwise a solution of ethyl chlorosulfonylacetate (1.15 g) in dichloromethane (5 ml) and pyridine (0.50 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature for 2 hours. After stirring, to the reaction mixture was added a saturated aqueous sodium chloride solution, and the resulting mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of ethyl acetate and hexane (2:3) as the eluent to afford the title compound (2.23 g, yield: 88 %) as a colorless oil. 1H NMR (400MHz, CDCl3) δ ppm : 1.34 (3H, t, J=7.0), 1.95-2.05 (2H, m), 2.06-2.15 (2H, m), 3.17 (2H, m), 3.50 (2H, m), 3.92 (2H, s), 4.30 (2H, q, J=7.0), 4.52 (1H, m), 6.86 (1H, t, J=7.5), 6.94-7.00 (2H, m), 6.97 (1H, d, J=9.0), 7.23 (1H, dd, J=9.0, 2.5), 7.25-7.30 (2H, m), 7.40 (1H, d, J=2.5).
	With pyridine In dichloromethane at 20℃;

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 140
[2]Location in patent: experimental part Noguchi, Tetsuji; Tanaka, Naoki; Nishimata, Toyoki; Goto, Riki; Hayakawa, Miho; Sugidachi, Atsuhiro; Ogawa, Taketoshi; Niitsu, Yoichi; Asai, Fumitoshi; Ishizuka, Tomoko; Fujimoto, Koichi [Chemical and Pharmaceutical Bulletin, 2009, vol. 57, # 1, p. 22 - 33]

28
[ 470477-21-5 ]
[ 55896-93-0 ]
[ 470477-22-6 ]

Yield	Reaction Conditions	Operation in experiment
89%	With pyridine In dichloromethane at 0 - 20℃;	36 Reference example 36; Ethyl N-[3-chloro-4-(1-methoxycarbonylmethylpiperidin-4-yloxy)phenyl]sulfamoylacetate To a solution of 3-chloro-4-(1-methoxycarbonylmethylpiperidin-4-yloxy)aniline (0.79 g) obtained in reference example 35 in dichloromethane (20 ml) were successively added dropwise ethyl chlorosulfonylacetate (0.37 ml) and pyridine (0.43 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature overnight and then evaporated in vacuo. The residue obtained was diluted with ethyl acetate, and the organic layer was washed with a saturated aqueous sodium hydrogencarbonate solution, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using ethyl acetate as the eluent to afford the title compound (1.06 g, yield: 89 %) as a yellow oil. 1H NMR (500MHz, CDCl3) δ ppm : 1.34 (3H, t, J=7.0), 1.90-1.99 (2H, m), 1.99-2.08 (2H, m), 2.53-2.62 (2H, m), 2.75-2.84 (2H, m), 3.27 (2H, s), 3.74 (3H, s), 3.91 (2H, s), 4.30 (2H, q, J=7.0), 4.41 (1H, m), 6.92 (1H, d, J=9.0), 7.20 (1H, dd, J=9.0, 2.5), 7.39 (1H, d, J=2.5).

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 141

29
[ 470477-27-1 ]
[ 55896-93-0 ]
[ 470477-28-2 ]

Yield	Reaction Conditions	Operation in experiment
57%	With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃;	42 Reference example 42; Ethyl N-[4-(1-carbamoylpiperidin-4-yloxy)-3-chlorophenyl]sulfamoylacetate To a solution of 4-(1-carbamoylpiperidin-4-yloxy)-3-chloroaniline (907 mg) obtained in reference example 41 in dichloromethane (20 ml) were successively added dropwise ethyl chlorosulfonylacetate (0.45 ml) and diisopropylethylamine (0.88 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature overnight. After stirring, furthermore ethyl chlorosulfonylacetate (0.05 ml) was added and the resulting mixture was stirred at room temperature for 2 hours and then evaporated in vacuo. The residue obtained was diluted with ethyl acetate, and the organic layer was washed with a saturated aqueous sodium hydrogencarbonate solution, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of dichloromethane and methanol (30:1 ~ 20:1) as the eluent to afford the title compound (809 mg, yield: 57 %) as a pale yellow amorphous solid. 1H NMR (400MHz, CDCl3) δ ppm : 1.34 (3H, t, J=7.0), 1.83-1.99 (4H, m), 3.47 (2H, m), 3.61 (2H, m), 3.92 (2H, s), 4.30 (2H, q, J=7.0), 4.58 (1H, m), 6.94 (1H, d, J=9.0), 7.23 (1H, dd, J=9.0, 2.5), 7.41 (1H, d, J=2.5) .

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 142

30
[ 470477-30-6 ]
[ 55896-93-0 ]
[ 470477-32-8 ]

Yield	Reaction Conditions	Operation in experiment
73%	With pyridine In dichloromethane at 0 - 20℃; for 1h;	46 Reference example 46; Ethyl N-[3-chloro-4-(1-methanesulfonylpiperidin-4-yloxy)phenyl]sulfamoylacetate To a solution of 3-chloro-4-(1-methanesulfonylpiperidin-4-yloxy)aniline (737 mg) obtained in reference example 45 in dichloromethane (20 ml) were successively added dropwise ethyl chlorosulfonylacetate (0.33 ml) and pyridine (0.39 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature for 1 hour. After stirring, the reaction mixture was diluted with ethyl acetate, and the organic layer was washed successively with a saturated aqueous sodium hydrogencarbonate solution and a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of ethyl acetate and hexane (3:2) as the eluent to afford the title compound (805 mg, yield: 73 %) as a pink amorphous solid. 1H NMR (400MHz, CDCl3) δ ppm: 1.26 (3H, t, J=7.0), 1.96-2.10 (4H, m), 2.82 (3H, s), 3.31 (2H, m), 3.47 (2H, m), 3.92 (2H, s), 4.30 (2H, q, J=7.0), 4.62 (1H, m), 6.93 (1H, d, J=9.0), 7.23 (1H, dd, J=9.0, 2.5), 7.42 (1H, d, J=2.5).

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 143

31
[ 470477-35-1 ]
[ 55896-93-0 ]
[ 470477-36-2 ]

Yield	Reaction Conditions	Operation in experiment
85%	With pyridine In dichloromethane at 0 - 20℃;	50 Reference example 50; Ethyl N-[3-chloro-4-[1-(2-pyridyl)piperidin-4-yloxy)phenyl]sulfamoylacetate To a solution of 3-chloro-4-[1-(2-pyridyl)piperidin-4-yloxy]aniline (680 mg) obtained in reference example 49 in dichloromethane (20 ml) were successively added dropwise ethyl chlorosulfonylacetate (0.32 ml) and pyridine (0.36 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature overnight. After stirring, the reaction mixture was diluted with ethyl acetate, and the organic layer was washed successively with a saturated aqueous sodium hydrogencarbonate solution and a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of ethyl acetate and hexane (1:1) as the eluent to afford the title compound (858 mg, yield: 85 %) as a pale yellow amorphous solid. 1H NMR (500MHz, CDCl3) δ ppm : 1.34 (3H, t, J=7.0), 1.88-1.98 (2H, m), 1.98-2.08 (2H, m), 3.56 (2H, m), 3.86 (2H, m), 3.92 (2H, s), 4.30 (2H, q, J=7.0), 4.58 (1H, m), 6.61 (1H, m), 6.70 (1H, d, J=8.5), 6.97 (1H, d, J=9.0), 7.23 (1H, dd, J=9.0, 2.5), 7.40 (1H, d, J=2.5), 7.48 (1H, m), 8.19 (1H, m).
	With pyridine In dichloromethane at 20℃;

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 144
[2]Location in patent: experimental part Noguchi, Tetsuji; Tanaka, Naoki; Nishimata, Toyoki; Goto, Riki; Hayakawa, Miho; Sugidachi, Atsuhiro; Ogawa, Taketoshi; Niitsu, Yoichi; Asai, Fumitoshi; Ishizuka, Tomoko; Fujimoto, Koichi [Chemical and Pharmaceutical Bulletin, 2009, vol. 57, # 1, p. 22 - 33]

32
[ 470477-39-5 ]
[ 55896-93-0 ]
[ 470477-40-8 ]

Yield	Reaction Conditions	Operation in experiment
78%	With pyridine In dichloromethane at 0 - 20℃; for 2h;	54 Reference example 54; Ethyl N-[3-chloro-4-[1-(3-pyridyl)piperidin-4-yloxy]phenyl]sulfamoylacetate To a solution of 3-chloro-4-[1-(3-pyridyl)piperidin-4-yloxy]aniline (1.38 g) obtained in reference example 53 in dichloromethane (20 ml) were successively added dropwise a solution of ethyl chlorosulfonylacetate (0.93 g) in dichloromethane (5 ml) and pyridine (0.37 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature for 2 hours and then evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of dichloromethane and methanol (9:1) as the eluent to afford the title compound (1.61 g, yield: 78 %) as a pale brown amorphous solid. 1H NMR (400MHz, CDCl3) δ ppm : 1.33 (3H, t, J=7.0), 1.97-2.15 (4H, m), 3.24 (2H, m), 3.51 (2H, m), 3.93 (2H, s), 4.29 (2H, q, J=7.0), 4.56 (1H, m), 6.97 (1H, d, J=9.0), 7.18 (1H, dd, J=8.5, 4.0), 7.21-7.28 (2H, m), 7.42 (1H, d, J=2.5), 8.10 (1H, d, J=4.0), 8.35 (1H,s).
	With pyridine In dichloromethane at 20℃;

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 145
[2]Location in patent: experimental part Noguchi, Tetsuji; Tanaka, Naoki; Nishimata, Toyoki; Goto, Riki; Hayakawa, Miho; Sugidachi, Atsuhiro; Ogawa, Taketoshi; Niitsu, Yoichi; Asai, Fumitoshi; Ishizuka, Tomoko; Fujimoto, Koichi [Chemical and Pharmaceutical Bulletin, 2009, vol. 57, # 1, p. 22 - 33]

33
[ 470477-44-2 ]
[ 55896-93-0 ]
[ 470477-46-4 ]

Yield	Reaction Conditions	Operation in experiment
70%	With pyridine In dichloromethane at 0 - 20℃;	58 Reference example 58; Ethyl N-[3-chloro-4-[1-(4-pyridyl)piperidin-4-yloxy]phenyl]sulfamoylacetate To a solution of 3-chloro-4-[1-(4-pyridyl)piperidin-4-yloxy]aniline (854 mg) obtained in reference example 57 in dichloromethane (20 ml) were successively added dropwise ethyl chlorosulfonylacetate (0.40 ml) and pyridine (0.45 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature overnight and then evaporated in vacuo. The residue obtained was neutralized with an aqueous potassium carbonate solution and extracted with ethyl acetate twice. The extract was washed with a saturated sodium hydrogencarbonate solution, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of dichloromethane and methanol (5:1 ~ 2:1) as the eluent to afford the title compound (888 mg, yield: 70 %) as a yellow amorphous solid. 1H NMR (500MHz, CDCl3) δ ppm : 1.33 (3H, t, J=7.0), 1.94-2.07 (4H, m), 3.47 (2H, m), 3.65 (2H, m), 3.93 (2H, s), 4.29 (2H, q, J=7.0), 4.63 (1H, m), 6.72 (2H, dd, J=5.0, 1.5), 6.96 (1H, d, J=9.0), 7.25 (1H, dd, J=9.0, 2.5), 7.43 (1H, d, J=2.5), 8.26 (2H, dd, J=5.0, 1.5).
	With pyridine In dichloromethane at 20℃;

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 146
[2]Location in patent: experimental part Noguchi, Tetsuji; Tanaka, Naoki; Nishimata, Toyoki; Goto, Riki; Hayakawa, Miho; Sugidachi, Atsuhiro; Ogawa, Taketoshi; Niitsu, Yoichi; Asai, Fumitoshi; Ishizuka, Tomoko; Fujimoto, Koichi [Chemical and Pharmaceutical Bulletin, 2009, vol. 57, # 1, p. 22 - 33]

34
[ 470477-49-7 ]
[ 55896-93-0 ]
[ 470477-50-0 ]

Yield	Reaction Conditions	Operation in experiment
85%	With pyridine In dichloromethane at 0 - 20℃; for 1h;	62 Reference example 62; Ethyl N-[3-chloro-4-[1-(2-pyrimidyl)piperidin-4-yloxy]phenyl]sulfamoylacetate To a solution of 3-chloro-4-[1-(2-pyrimidyl)piperidin-4-yloxy]aniline (1.01 g) obtained in reference example 61 in dichloromethane (30 ml) were successively added dropwise ethyl chlorosulfonylacetate (0.47 ml) and pyridine (0.53 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature for 1 hour and then evaporated in vacuo. The residue obtained was neutralized with a saturated aqueous sodium hydrogencarbonate solution and extracted with ethyl acetate. The extract was washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of hexane and ethyl acetate (2:1 ~ 1:1) as the eluent to afford the title compound (1.29 g, yield: 85 %) as a pale brown amorphous solid. 1H NMR (500MHz, CDCl3) δ ppm : 1.34 (3H, t, J=7.0), 1.85-1.95 (2H, m), 1.95-2.05 (2H, m), 3.85 (2H, m), 3.93 (2H, s), 4.09 (2H, m), 4.30 (2H, q, J=7.0), 4.61 (1H, m), 6.48 (1H, t, J=4.5), 6.98 (1H, d, J=9.0), 7.23 (1H, dd, J=9.0, 2.5), 7.41 (1H, d, J=2.5), 8.32 (2H, d, J=4.5).

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 147-148

35
[ 470477-53-3 ]
[ 55896-93-0 ]
[ 470477-54-4 ]

Yield	Reaction Conditions	Operation in experiment
60%	With pyridine In dichloromethane at 0 - 20℃; for 3h;	66 Reference example 66; Ethyl N-[3-chloro-4-[1-(3-pyridylmethyl)piperidin-4-yloxy]phenyl]sulfamoylacetate To a solution of 3-chloro-4-[1-(3-pyridylmethyl)piperidin-4-yloxy]aniline (874 mg) obtained in reference example 65 in dichloromethane (20 ml) were successively added dropwise ethyl chlorosulfonylacetate (0.39 ml) and pyridine (0.44 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature for 3 hour and evaporated in vacuo. The residue obtained was neutralized with a saturated aqueous sodium hydrogencarbonate solution and extracted with ethyl acetate. The extract was washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of dichloromethane and methanol (20:1 ~ 10:1) as the eluent to afford the title compound (770 mg, yield: 60 %) as a yellow amorphous solid. 1H NMR (500MHz, CDCl3) δ ppm : 1.33 (3H, t, J=7.0), 1.84-1.93 (2H, m), 1.93-2.02 (2H, m), 2.38 (2H, m), 2.72 (2H, m), 3.55 (2H, s), 3.91 (2H, s), 4.29 (2H, q, J=7.0), 4.39 (1H, m), 6.92 (1H, d, J=9.0), 7.20 (1H, dd, J=9.0, 2.5), 7.27 (1H, m), 7.39 (1H, d, J=2.5), 7.69 (1H, d, J=7.5), 8. 51 (1H, d, J=3.5), 8.56 (1H, s).

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 148-149

36
[ 470477-59-9 ]
[ 55896-93-0 ]
[ 470477-60-2 ]

Yield	Reaction Conditions	Operation in experiment
82%	With pyridine In dichloromethane at 0 - 20℃; for 2h;	76 Reference example 76; Ethyl N-[3-chloro-4-[1-[2-(2-pyridyl)ethyl]piperidin-4-yloxy]phenyl]sulfamoylacetate To a solution of 3-chloro-4-[1-[2-(2-pyridyl)ethyl]piperidin-4-yloxy]aniline (1.26 g) obtained in reference example 75 in dichloromethane (30 ml) were successively added dropwise ethyl chlorosulfonylacetate (0.54 ml) and pyridine (0.61 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature for 2 hours and evaporated in vacuo. The residue obtained was neutralized with a saturated aqueous sodium hydrogencarbonate solution and extracted with ethyl acetate three times, and the extract was dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of dichloromethane and methanol (10:1 ~ 5:1) as the eluent to afford the title compound (1.50 g, yield: 82 %) as a pale yellow amorphous solid. 1H NMR (500MHz, CDCl3) δ ppm : 1.33 (3H, t, J=7.0), 1.86-1.97 (2H, m), 1.97-2.08 (2H, m), 2.50 (2H, m), 2.77-2.92 (4H, m), 3.03 (2H, m), 3.92 (2H, s), 4.29 (2H, q, J=7.0), 4.40 (1H, m), 6.93 (1H, d, J=9.0), 7.13 (1H, m), 7.21 (1H, dd, J=9.0, 2.5), 7.17-7.24 (1H, m), 7.40 (1H, d, J=2.5), 7.61 (1H, m), 8.53 (1H, d, J=5.0).

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 151

37
[ 470477-63-5 ]
[ 55896-93-0 ]
[ 470477-64-6 ]

Yield	Reaction Conditions	Operation in experiment
37%	With pyridine In dichloromethane at 0 - 20℃; for 3h;	80 Reference example 80; Ethyl N-[3-chloro-4-(1-cyclopentylpiperidin-4-yloxy)phenyl]sulfamoylacetate To a solution of 3-chloro-4-(1-cyclopentylpiperidin-4-yloxy)aniline (1.97 g) obtained in reference example 79 in dichloromethane (40 ml) were successively added dropwise ethyl chlorosulfonylacetate (0.94 ml) and pyridine (1.08 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature,for 3 hours and evaporated in vacuo. The residue obtained was diluted with ethyl acetate, and the organic layer was washed successively with a saturated aqueous sodium hydrogencarbonate solution and a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixture of dichloromethane and methanol (25:1 ~ 10:1) as the eluent to afford the title compound (1.09 g, yield: 37 %) as a pale brown amorphous solid. 1H NMR (500MHz, CDCl3) δ ppm : 1.33 (3H, t, J=7.0), 1.38-1.62 (4H, m), 1.62-1.77 (2H, m), 1.80-1.96 (4H, m), 1.96-2.09 (2H, m), 2.47 (2H, m), 2.59 (1H, m), 2.79 (2H, m), 3.92 (2H, s), 4.29 (2H, q, J=7.0), 4.39 (1H, m), 6.92 (1H, d, J=9.0), 7.20 (1H, dd, J=9.0, 2.5), 7.39 (1H, d, J=2.5).
	With pyridine In dichloromethane at 20℃;

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 152
[2]Location in patent: experimental part Noguchi, Tetsuji; Tanaka, Naoki; Nishimata, Toyoki; Goto, Riki; Hayakawa, Miho; Sugidachi, Atsuhiro; Ogawa, Taketoshi; Niitsu, Yoichi; Asai, Fumitoshi; Ishizuka, Tomoko; Fujimoto, Koichi [Chemical and Pharmaceutical Bulletin, 2009, vol. 57, # 1, p. 22 - 33]

38
[ 470477-68-0 ]
[ 55896-93-0 ]
[ 470477-69-1 ]

Yield	Reaction Conditions	Operation in experiment
73%	With pyridine In dichloromethane at 0 - 20℃; for 1h;	88 Reference example 88; Ethyl N-[3-chloro-4-(1,2-dimethylpiperidin-4-yloxy)phenyl]sulfamoylacetate To a solution of 3-chloro-4-(1,2-dimethylpiperidin-4-yloxy)aniline (690 mg) obtained in reference example 87 in dichloromethane (20 ml) were successively added dropwise ethyl chlorosulfonylacetate (0.40 ml) and pyridine (0.25 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature for 1 hour and evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of dichloromethane and methanol (9:1 ~ 3:1) as the eluent to afford the title compound (800 mg, yield: 73 %) as a yellow amorphous solid. 1H NMR (500MHz, CDCl3) δ ppm : 1.18 (3H, t, J=7.0), 1.26 (3H, m), 1.55-1.70 (1H, m), 1.75-1.90 (1H, m), 2.15-2.30 (2H, m), 2.55-2.75 (3H, m), 2.80-3.30 (3H, m), 4.11 (2H, q, J=7.0), 4.20 (2H, s), 4.45-4.55 (1H, m), 7.17 (1H, dd, J=9.0, 2.5), 7.27 (1H, d, J=9.0), 7.29 (1H, d, J=2.5).

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 155

39
[ 470477-72-6 ]
[ 55896-93-0 ]
[ 470477-73-7 ]

Yield	Reaction Conditions	Operation in experiment
82%	With pyridine In dichloromethane at 0 - 20℃; for 0.5h;	92 Reference example 92; Ethyl N-(3-chloro-4-methoxymethoxyphenyl)sulfamoylacetate To a solution of 3-chloro-4-methoxymethoxyaniline (5.4 g) obtained in reference example 91 in dichloromethane (50 ml) were successively added dropwise ethyl chlorosulfonylacetate (4.7 ml) and pyridine (2.9 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature for 30 minutes. After stirring, to the reaction mixture was added water, and the resulting mixture was extracted with ethyl acetate. The extract was washed successively with water and a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of dichloromethane and methanol (19:1) as the eluent to afford the title compound (8.0 g, yield: 82 %) as a reddish brown oil. 1H NMR (500MHz, CDCl3) δ ppm : 1.34 (3H, t, J=7.0), 3.52 (3H, s), 3.92 (2H, s), 4.30 (2H, q, J=7.0), 5.24 (2H, s), 7.15-7.25 (2H, m), 7.41 (1H, m).

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 156

40
[ 55896-93-0 ]
[ 138227-63-1 ]
[ 290332-75-1 ]

Yield	Reaction Conditions	Operation in experiment
75%	With pyridine; In dichloromethane; at 0 - 20℃;	To a solution of 4-(1-t-butoxycarbonylpiperidin-4-yloxy)aniline (4.39 g) obtained in reference example 106 in dichloromethane (30 ml) were successively added dropwise ethyl chlorosulfonylacetate (2.4 ml) and pyridine (2.4 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature overnight and then evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of hexane and ethyl acetate (3:2) as the eluent to afford the title compound (4.96 g, yield: 75 %) as a pale red oil. 1H NMR (400MHz, CDCl3) delta ppm : 1.33 (3H, t, J=7.0), 1.47 (9H, s), 1.75 (2H, m), 1.90 (2H, m), 3:34 (2H, m), 3.69 (2H, m), 3.89 (2H, s), 4.29 (2H, q, J=7.0), 4.44 (1H, m), 6.89 (2H, d, J=8.5), 7.27 (2H, d, J=8.5).

Reference： [1]Chemical and Pharmaceutical Bulletin,2008,vol. 56,p. 758 - 770
[2]Patent: EP1375482,2004,A1 .Location in patent: Page 159

41
[ 947176-00-3 ]
[ 55896-93-0 ]
ethyl N-[3-chloro-4-(tropan-3-yloxy)phenyl]sulfamoylacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With pyridine In dichloromethane at 0 - 20℃; for 3.5h;	125 Reference example 125; Ethyl N-[3-chloro-4-(tropan-3-yloxy)phenyl]sulfamoylacetate To a solution of 3-chloro-4-(tropan-3-yloxy)aniline (2.5 g) obtained in reference example 124 in dichloromethane (50 ml) were successively added dropwise ethyl chlorosulfonylacetate (1.5 ml) and pyridine (0.9 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature for 3.5 hours and then evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of dichloromethane and methanol (4:1) as the eluent to afford the title compound (3.5 g, yield: 89 %) as a pale brown amorphous solid. 1H NMR (500MHz, CDCl3) δ ppm : 1.32 (3H, t, J=7.0), 1.95-2.05 (2H, m), 2.20-2.25 (2H, m), 2.30-2.75 (4H, m), 2.84 (3H, s), 3.89 (2H, m), 3.98 (2H, s), 4.28 (2H, q, J=7.0), 4.49 (1H, m), 6.95 (1H, d, J=8.5), 7.25 (1H, dd, J=2.5, 8.5), 7.45 (1H, d, J=2.5).

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1375482, 2004, A1 Location in patent: Page 164

42
[ 55896-93-0 ]
[ 540-37-4 ]
[ 658709-20-7 ]

Yield	Reaction Conditions	Operation in experiment
92%	Stage #1: ethyl 2-(chlorosulfonyl)acetate; p-aminoiodobenzene With triethylamine In ethyl acetate at 20℃; for 72h; Stage #2: With hydrogenchloride In water; ethyl acetate	1.1 To a solution of 4-iodoaniline (2.01 g) and triethylamine (1.7 mL) in ethyl acetate (100 [ML)] was added chlorosulfonyl-acetic acid ethyl ester (2.21 g). The reaction was stirred at room temperature under nitrogen for three days. Water was added, then 1 M hydrochloric acid to aid breaking the resulting emulsion. The organic layer was next washed with sodium bicarbonate and brine, dried [(MGS04)] and evaporated to an oil. The material was dissolved in ethyl acetate and passed through a column of silica gel. The resulting eluent was evaporated to a brown solid (3.1 g, 92% yield). MS (APCI-) [17IZ] 368. 1H-NMR (CDC13) 8 7.67 (d, [2H),] 7.08 (d, [2H),] 6.90 (s, [1H),] 4.27 (q, 2H), 3.91 (s, 2H), 1. [31] (t, 3H).

Reference： [1]Current Patent Assignee: PFIZER INC - WO2004/14388, 2004, A1 Location in patent: Page/Page column 230-231

43
[ 55896-93-0 ]
[ 876-30-2 ]
[ 141-78-6 ]
[ 337522-37-9 ]

Yield	Reaction Conditions	Operation in experiment
67%	With pyridine In hexane; dichloromethane; water	R.52 Ethyl N-(4-Methoxymethoxyphenyl)sulfamoylacetate Reference Example 52 Ethyl N-(4-Methoxymethoxyphenyl)sulfamoylacetate To a solution of 4-methoxymethoxyaniline (20.9 g) and pyridine (33 ml) in dichloromethane (400 ml) was added dropwise ethyl chlorosulfonylacetate (18.0 ml) in an ice bath and the mixture was stirred at room temperature overnight. After addition of water, the reaction mixture was extracted with ethyl acetate. The extract was washed with brine. The organic layer was dried over anhydrous magnesium sulfate, filtered and the filtrate concentrated in vacuo. The residue was purified by chromatography on a silica gel column using hexane/ethyl acetate=3/2 as an eluant to give the desired compound (28.0 g, yield 67%) as a brown oil. 1H NMR (270 MHz, CDCl3) δ ppm: 1.33 (3H, t, J=7.0), 3.48 (3H, s), 3.90 (2H, s), 4.29 (2H, q, J=7.0), 5.16 (2H, s), 7.03 (2H, d, J=9.0), 7.28 (2H, d, J=9.0).

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - US6555556, 2003, B1

44
[ 138227-69-7 ]
[ 55896-93-0 ]
[ 141-78-6 ]
[ 337519-92-3 ]

Yield	Reaction Conditions	Operation in experiment
76%	With pyridine In methanol; hexane; dichloromethane	R.36 Ethyl N-[4-(1-t-Butoxycarbonylpiperidin-4-yloxy)-3-methylphenyl]sulfamoylacetate Reference Example 36 Ethyl N-[4-(1-t-Butoxycarbonylpiperidin-4-yloxy)-3-methylphenyl]sulfamoylacetate To a solution of 4-(1-t-butoxycarbonylpiperidin-4-yloxy)-3-methylaniline (1.63 g) and pyridine (0.81 ml) in dichloromethane (30 ml) was added dropwise ethyl chlorosulfonylacetate (0.86 ml) in an ice bath and the mixture was stirred at room temperature for 5 hours. After addition of methanol (0.5 ml), the reaction mixture was concentrated in vacuo. The residue was purified by chromatography on a silica gel column using hexane/ethyl acetate=3/2 as an eluant to give the desired compound (1.84 g, yield 76%) as a pale brown amorphous solid. 1H NMR (500 MHz, CDCl3) δ ppm: 1.34 (3H, t, J=7.0), 1.47 (9H, s), 1.78 (2H, m), 1.89 (2H, m), 2.22 (3H, s), 3.43 (2H, m), 3.62 (2H, m), 3.90 (2H, s), 4.29 (2H, q, J=7.0), 4.48 (1H, m), 6.79 (1H, d, J=8.0), 7.12 (2H, m).

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - US6555556, 2003, B1

45
[ 55896-93-0 ]
[ 141-78-6 ]
[ 325457-62-3 ]
[ 337519-90-1 ]

Yield	Reaction Conditions	Operation in experiment
73%	With pyridine In hexane; dichloromethane	R.32 Ethyl N-[4-(1-t-Butoxycarbonylpiperidin-4-yloxy)-3-trifluoromethylphenyl]sulfamoylacetate Reference Example 32 Ethyl N-[4-(1-t-Butoxycarbonylpiperidin-4-yloxy)-3-trifluoromethylphenyl]sulfamoylacetate To a solution of 4-(1-t-butoxycarbonylpiperidin-4-yloxy)-3-trifluoromethylaniline (1.69 g) and pyridine (0.49 ml) in dichloromethane (20 ml) was added dropwise ethyl chlorosulfonylacetate (0.76 ml) in an ice bath and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated in vacuo. The residue was purified by chromatography on a silica gel column using hexane/ethyl acetate=3/2 as an eluant to give the desired compound (1.74 g, yield 73%) as a pale red oil. 1H NMR (500 MHz, CDCl3) δ ppm: 1.34 (3H, t, J=7.0), 1.48 (9H, s), 1.83-1.94 (4H, m), 3.48-3.60 (4H, m), 3.91 (2H, s), 4.31 (2H, q, J=7.0), 4.65 (1H, m), 6.99 (1H, d, J=9.0), 7.52 (1H, dd, J=9.0, 2.5), 7.56 (1H, d, J=2.5).

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - US6555556, 2003, B1

46
[ 55896-93-0 ]
[ 141-78-6 ]
[ 250372-00-0 ]
[ 337519-85-4 ]

Yield	Reaction Conditions	Operation in experiment
71%	With pyridine In hexane; dichloromethane	R.24 Ethyl N-[4-(1-t-Butoxycarbonylpiperidin-4-yloxy)-3-fluorophenyl]sulfamoylacetate Reference Example 24 Ethyl N-[4-(1-t-Butoxycarbonylpiperidin-4-yloxy)-3-fluorophenyl]sulfamoylacetate To a solution of 4-(1-t-butoxycarbonylpiperidin-4-yloxy)-3-fluoroaniline (1.49 g) and pyridine (0.77 ml) in dichloromethane (30 ml) was added dropwise ethyl chlorosulfonylacetate (0.77 ml) in an ice bath and the mixture was stirred at room temperature for 7 hours. The reaction mixture was concentrated in vacuo. The residue was purified by chromatography on a silica gel column using hexane/ethyl acetate=3/2 as an eluant to give the desired compound (1.58 g, yield 71%) as a pale red oil. 1H NMR (500 MHz, CDCl3) δ ppm: 1.33 (3H, t, J=7.0), 1.47 (9H, s), 1.77 (2H, m), 1.90 (2H, m), 3.32 (2H, m), 3.72 (2H, m), 3.92 (2H, s), 4.29 (2H, q, J=7.0), 4.42 (1H, m), 6.97 (1H, dd, J=9.0, 8.5), 7.04 (1H, dd, J=9.0, 3.0), 7.17 (1H, dd, J=11.5, 3.0).

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - US6555556, 2003, B1

47
[ 55896-93-0 ]
[ 141-78-6 ]
[ 337520-13-5 ]
[ 337520-14-6 ]

Yield	Reaction Conditions	Operation in experiment
90%	With pyridine In hexane; dichloromethane	R.60 Ethyl N-[4-(1-t-Butoxycarbonylpiperidin-4-yloxy)-3-ethoxycarbonylphenyl]sulfamoylacetate Reference Example 60 Ethyl N-[4-(1-t-Butoxycarbonylpiperidin-4-yloxy)-3-ethoxycarbonylphenyl]sulfamoylacetate To a solution of 4-(1-t-butoxycarbonylpiperidin-4-yloxy)-3-ethoxycarbonylaniline (4.6 g) and pyridine (2.0 ml) in dichloromethane (70 ml) was added dropwise ethyl chlorosulfonylacetate (2.5 ml) in an ice bath and the mixture was stirred at room temperature for 6 hours. The reaction mixture was concentrated in vacuo. The residue was suspended in a mixture of hexane/ethyl acetate=1/1 and filtered. The filtrate was purified by chromatography on a silica gel column using hexane/ethyl acetate=1/1 as an eluant to give the desired compound (5.9 g, yield 90%) as an orange amorphous solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.34 (3H, t, J=7.0), 1.37 (3H, t, J=7.0), 1.47 (9H, s), 1.75-1.95 (4H, m), 3.45-3.55 (2H, m), 3.55-3.65 (2H, m), 3.91 (2H, s), 4.30 (2H, q, J=7.0), 4.35 (2H, q, J=7.0), 4.59 (1H, m), 6.97 (1H, d, J=9.0), 7.47 (1H, dd, J=9.0, 3.0), 7.70 (1H, d, J=3.0).

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - US6555556, 2003, B1

48
[ 337520-17-9 ]
[ 55896-93-0 ]
[ 141-78-6 ]
[ 337520-18-0 ]

Yield	Reaction Conditions	Operation in experiment
74%	With pyridine In hexane; dichloromethane	R.64 Ethyl N-[3-Bromo-4-(1-t-butoxycarbonylpiperidin-4-yloxy)phenyl]sulfamoylacetate Reference Example 64 Ethyl N-[3-Bromo-4-(1-t-butoxycarbonylpiperidin-4-yloxy)phenyl]sulfamoylacetate To a solution of 3-bromo-4-(1-t-butoxycarbonylpiperidin-4-yloxy)aniline (2.0 g) and pyridine (0.9 ml) in dichloromethane (60 ml) was added dropwise ethyl chlorosulfonylacetate (0.9 ml) in an ice bath and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated in vacuo. The residue was purified by chromatography on a silica gel column using hexane/ethyl acetate=1/1 as an eluant to give the desired compound (2.1 g, yield 74%) as a yellow amorphous solid. 1H NMR (500 MHz, CDCl3) δ ppm: 1.34 (3H, t, J=7.0), 1.47 (9H, s), 1.75-1.95 (4H, m), 3.45-3.55 (2H, m), 3.55-3.65 (2H, m), 3.92 (2H, s), 4.29 (2H, q, J=7.0), 4.55 (1H, m), 6.85-6.95 (2H, m), 7.56 (1H, m).

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - US6555556, 2003, B1

49
[ 337520-21-5 ]
[ 55896-93-0 ]
[ 141-78-6 ]
[ 337520-22-6 ]

Yield	Reaction Conditions	Operation in experiment
80%	With pyridine In dichloromethane	R.69 Ethyl N-[4-(1-t-Butoxycarbonylpiperidin-4-yloxy)-3-isopropylphenyl]sulfamoylacetate Reference Example 69 Ethyl N-[4-(1-t-Butoxycarbonylpiperidin-4-yloxy)-3-isopropylphenyl]sulfamoylacetate To a solution of 4-(1-t-butoxycarbonylpiperidin-4-yloxy)-3-isopropylaniline (2.8 g) and pyridine (1.4 ml) in dichloromethane (80 ml) was added dropwise ethyl chlorosulfonylacetate (1.5 ml) in an ice bath and the mixture was stirred at room temperature for 4 hours. The reaction mixture was concentrated in vacuo. The residue was purified by chromatography on a silica gel column using dichloromethane/ethyl acetate=19/1 as an eluant to give the desired compound (3.3 g, yield 80%) as a yellow amorphous solid. 1H NMR (500 MHz, CDCl3) δ ppm: 1.20 (6H, d, J=7.0), 1.37 (3H, t, J=7.0), 1.48 (9H, s), 1.75-1.85 (2H, m), 1.85-1.95 (2H, m), 3.30 (1H, m), 3.40-3.50 (2H, m), 3.55-3.65 (2H, m), 3.90 (2H, s), 4.30 (2H, q, J=7.0), 4.50 (1H, m), 6.80 (1H, d, J=9.0), 7.13 (1H, dd, J=9.0, 3.0), 7.17 (1H, d, J=3.0).

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - US6555556, 2003, B1

50
[ 337520-63-5 ]
[ 55896-93-0 ]
[ 141-78-6 ]
[ 337520-64-6 ]

Yield	Reaction Conditions	Operation in experiment
70%	With pyridine In hexane; dichloromethane; water	R.114 Ethyl N-[4-(1-t-Butoxycarbonylpiperidin-4-yloxy)-3,5-dimethylphenyl]sulfamoylacetate Reference Example 114 Ethyl N-[4-(1-t-Butoxycarbonylpiperidin-4-yloxy)-3,5-dimethylphenyl]sulfamoylacetate To a solution of 4-(1-t-butoxycarbonylpiperidin-4-yloxy)-3,5-dimethylaniline (1.94 g) and pyridine (0.98 ml) in dichloromethane (30 ml) was added dropwise ethyl chlorosulfonylacetate (0.97 ml) in an ice bath and the mixture was stirred at room temperature for 14 hours. After addition of water, the reaction mixture was extracted with ethyl acetate. The extract was washed with brine. The organic layer was dried over anhydrous magnesium sulfate, filtered and the filtrate concentrated in vacuo. The residue was purified by chromatography on a silica gel column using hexane/ethyl acetate=2/1 as an eluant to give the desired compound (2.00 g, yield 70%) as a pale yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm: 1.33 (3H, t, J=7.0), 1.47 (9H, s), 1.69 (2H, m), 1.91 (2H, m), 2.26 (6H, s), 2.89 (2H, m), 3.90 (1H, m), 3.93 (2H, s), 4.03 (2H, m), 4.29 (2H, q, J=7.0), 6.98 (2H, s).

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - US6555556, 2003, B1

51
[ 55896-93-0 ]
[ 141-78-6 ]
[ 138227-63-1 ]
[ 290332-75-1 ]

Yield	Reaction Conditions	Operation in experiment
75%	With pyridine; In methanol; hexane; dichloromethane;	Reference Example 12 Ethyl N-[4-(1-t-Butoxycarbonylpiperidin-4-yloxy)phenyl]sulfamoylacetate To a solution of 4-(1-t-butoxycarbonylpiperidin-4-yloxy)aniline (4.39 g) and pyridine (2.4 ml) in dichloromethane (30 ml) was added dropwisely ethyl chlorosulfonylacetate (2.4 ml) in an ice bath and the mixture was stirred at room temperature for 13 hours. After addition of methanol (0.5 ml), the reaction mixture was concentrated in vacuo. The residue was purified by chromatography on a silica gel column using hexane/ethyl acetate=3/2 as an eluant to give the desired compound (4.96 g, yield 75%) as a pale red oil. 1H NMR (400 MHz, CDCl3) delta ppm 1.33 (3H, t, J=7.0), 1.47 (9H, s), 1.75 (2H, m), 1.90 (2H, m), 3.34 (2H, m), 3.69 (2H, m), 3.89 (2H, s), 4.29 (2H, q, J=7.0), 4.44 (1H, m), 6.89 (2H, d, J=8.5), 7.27 (2H, d, J=8.5).

Reference： [1]Patent: US6555556,2003,B1

52
[ 337520-59-9 ]
[ 55896-93-0 ]
[ 337520-60-2 ]

Yield	Reaction Conditions	Operation in experiment
95%	With pyridine In hexane; dichloromethane; ethyl acetate	R.110 Ethyl N-[4-(1-t-Butoxycarbonylpiperidin-4-yloxy)-3,5-dichlorophenyl]sulfamoylacetate Reference Example 110 Ethyl N-[4-(1-t-Butoxycarbonylpiperidin-4-yloxy)-3,5-dichlorophenyl]sulfamoylacetate To a solution of 4-(1-t-butoxycarbonylpiperidin-4-yloxy)-3,5-dichloroaniline (1.40 g) and pyridine (0.63 ml) in dichloromethane (30 ml) was added dropwise ethyl chlorosulfonylacetate (0.57 ml) in an ice bath and the mixture was stirred at room temperature for 1.5 hours. The reaction mixture was partitioned between ethyl acetate and water. The extract was washed with brine. The organic layer was dried over anhydrous magnesium sulfate, filtered and the filtrate concentrated in vacuo. The residue was purified by chromatography on a silica gel column using hexane/ethyl acetate 2/1 as an eluant to give the desired compound (1.89 g, yield 95%) as a pale yellow amorphous solid. 1H NMR (400 MHz, CDCl3) δ ppm: 1.34 (3H, t, J=7.0), 1.47 (9H, s), 1.80-2.00 (4H, m), 3.14 (2H, m), 3.92 (2H, m), 3.96 (2H, s), 4.30 (2H, q, J=7.0), 4.37 (1H, m), 7.33 (2H, s).
	With pyridine In dichloromethane

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - US6555556, 2003, B1
[2]Location in patent: experimental part Noguchi, Tetsuji; Tanaka, Naoki; Nishimata, Toyoki; Goto, Riki; Hayakawa, Miho; Sugidachi, Atsuhiro; Ogawa, Taketoshi; Asai, Fumitoshi; Fujimoto, Koichi [Chemical and Pharmaceutical Bulletin, 2008, vol. 56, # 6, p. 758 - 770]

53
[ 136079-13-5 ]
[ 55896-93-0 ]
Ethyl [(3,4-dihydro-1'-[2-(benzofurazan-5-yl)-ethyl]-4-oxo-spiro[(2H)-1-benzopyran-2,4'-piperidine]-6-yl)amino]sulfonyl acetate hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With pyridine In ethyl acetate; N,N-dimethyl-formamide	Ethyl [(3,4-dihydro-1'-[2-(benzofurazan-5-yl)-ethyl]-4-oxo-spiro[(2H)-1-benzopyran-2,4'-piperidine]-6-yl)amino]sulfonyl acetate hydrochloride Ethyl [(3,4-dihydro-1'-[2-(benzofurazan-5-yl)-ethyl]-4-oxo-spiro[(2H)-1-benzopyran-2,4'-piperidine]-6-yl)amino]sulfonyl acetate hydrochloride Ethyl chlorosulfonylacetate (140 mg, 0.75 mmol) in DMF (1 ml) was added dropwise to a stirred solution of 6-amino-3,4-dihydro-1'-[2-(benzofurazan-5-yl)-ethyl]-spiro[(2H)-1-benzopyran-2,4'-piperidine]-4-one (189 mg, 0.5 mmol) and pyridine (40 mg, 3 mmol) in DMF (5 ml). The mixture was stirred for 4 hours, then additional ethyl chlorosulfonylacetate (46 mg, 0.25 mmol) was added. The mixture was stirred for 1 hour, poured into aqueous sodium hydrogen carbonate (saturated, 25 ml) and extracted with dichloromethane (3*25 ml). The combined organic fractions were dried (Na2 SO4) and evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluding with CH2 Cl2 /MeOH/NH3 (Aq.) (97:3:0.3) to give a yellow foam which was dissolved in ethyl acetate (2 ml) and treated with ethanolic HCl (6N, 0.5 ml). The mixture was stirred for 1 hour, cooled and the solid was collected and dried in vacuo to give the hydrochloride as a white solid (171 mg, 61%), m.p. 250°-251° C. Anal. Calc'd. for C25 H29 ClN4 O7 S: C, 53.14; H, 5.17; N, 9.92. Found: C, 53.00; H, 5.39; N, 9.86.

Reference： [1]Current Patent Assignee: MERCK & CO INC - US5206240, 1993, A

54
[ 55896-93-0 ]
[ 367-25-9 ]
2-[N (2,4-Difluorophenyl)sulfamoyl]-acetic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56.55%	With pyridine; hydrogenchloride In 1,1-dichloroethane	1 2-[N (2,4-Difluorophenyl)sulfamoyl]-acetic acid methyl ester Example 1 2-[N (2,4-Difluorophenyl)sulfamoyl]-acetic acid methyl ester 3.87 g (30 mmol) of 2,4-difluoroaniline is dissolved, with exclusion of moisture, in 80 ml of dichloroethane, 2.5 ml (30 mmol) of pyridine is added and the solution is cooled to 0° C. 5.18 g (30 mmol) of chlorosulfonyl ethyl acetate, dissolved in 20 ml of dichloroethane, is instilled in the cooled solution, stirred for 1 hour at 0° C. and 12 hours at room temperature. The reaction solution is then shaken out with 2N hydrochloric acid, the phases are separated, the organic phase is dried on sodium sulfate, concentrated by evaporation in a vacuum and the oily residue is chromatographed on 200 g of silica gel 60 (Merck) with ethyl acetate/hexane. 4.5 g (16.97 mmol)=56.55% of the theoretical yield of the title compound is obtained as oil.

Reference： [1]Current Patent Assignee: BAYER AG - US5130119, 1992, A

55
[ 220220-24-6 ]
[ 55896-93-0 ]
[ 56553-60-7 ]
[ 179756-49-1 ]
ethyl [N-[4-(4-t-butoxycarbonyl-hexahydro-1H-1,4-diazepin-1-yl)-3-fluorophenyl]-N-[(7-cyano-2-naphthyl)methyl]sulfamoyl]acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; acetic acid;palladium-carbon; In ethanol; 1,2-dichloro-ethane;	REFERENCE EXAMPLE 37 1.62 g of 4-t-butoxycarbonyl-1-(2-fluoro-4-nitro-phenyl)hexahydro-1H-1,4-diazepine obtained in Reference Example 13 was suspended in 48 ml of ethanol, to which was added 160 mg of 10% palladium-carbon, and stirred in a hydrogen atmosphere at room temperature for 2 hours. The reaction mixture was filtered, and then evaporated. The resulting residue weighed 1.62 g. 0.61 g of this was dissolved in 20 ml of 1,2-dichloroethane, to which were added 357 mg of 7-formyl-2-naphthalenecarbonitrile, 1.2 g of acetic acid and 823 mg of sodium triacetoxy-borohydride in that order, and stirred at room temperature for 2 hours. The reaction mixture was washed with aqueous 10% sodium carbonate and saturated saline in that order, dried over anhydrous sodium sulfate, and then evaporated. The resulting residue was dissolved in 20 ml of 1,2-dichloroethane, to which were added 467 mg of pyridine and 560 mg of ethyl chlorosulfonylacetate at 0 C., and stirred for 1 hour. One ml of ethanol was added to this, and stirred for 1 hours, and then, the reaction mixture was concentrated. The resulting residue was purified through silica gel column chromatography using an eluent solvent of hexane/ethyl acetate (3/1) to obtain 1.08 g of ethyl [N-[4-(4-t-butoxycarbonyl-hexahydro-1H-1,4-diazepin-1-yl)-3-fluorophenyl]-N-[(7-cyano-2-naphthyl)methyl]sulfamoyl]acetate.

Reference： [1]Patent: US6333320,2001,B1

56
[ 55896-93-0 ]
[ 96649-05-7 ]
[ 1049708-54-4 ]

Yield	Reaction Conditions	Operation in experiment
97%	With pyridine In dichloromethane at 0℃; for 2.5h;

Reference： [1]Location in patent: experimental part Noguchi, Tetsuji; Tanaka, Naoki; Nishimata, Toyoki; Goto, Riki; Hayakawa, Miho; Sugidachi, Atsuhiro; Ogawa, Taketoshi; Asai, Fumitoshi; Fujimoto, Koichi [Chemical and Pharmaceutical Bulletin, 2008, vol. 56, # 6, p. 758 - 770]

57
[ 55896-93-0 ]
[ 94792-93-5 ]
[ 1388859-80-0 ]

Yield	Reaction Conditions	Operation in experiment
48%	With dmap; triethylamine In dichloromethane at 0 - 20℃; for 2h; Inert atmosphere;	Typical Procedure for the Preparation of Propargyl Sulfonates General procedure: To a solution of 1a (2.28 g, 10.0 mmol), p-toluenesulfonyl chloride (2.09 g, 11.0 mmol), and 4-(N,N-dimethyl)pyridine (0.024 g, 0.20 mmol) in CH2Cl2 (20 mL) was added at 0 °C triethylamine (1.67 mL, 12.0 mmol) and the resultant mixture was stirred at room temperature for 2 h. The reaction mixture was quenched with saturated NH4Cl aq. (30 mL) and extracted with CH2Cl2 (3 × 70 mL). Concentration by rotary evaporator after dried over Na2SO4 furnished a crude material which was purified by silica gel column chromatography (hexane:EtOAc = 15:1) to give 3.59 g (9.39 mmol) of pure propargyl tosylate 2aa in 94% yield.

Reference： [1]Yamazaki, Takashi; Watanabe, Yohsuke; Yoshida, Nao; Kawasaki-Takasuka, Tomoko [Tetrahedron, 2012, vol. 68, # 33, p. 6665 - 6673]

58
[ 55896-93-0 ]
[ 104-94-9 ]
[ 106-93-4 ]
[ 1318758-32-5 ]

Yield	Reaction Conditions	Operation in experiment
27%	Stage #1: ethyl 2-(chlorosulfonyl)acetate; 4-methoxy-aniline With pyridine In acetonitrile at 0 - 20℃; for 0.333333h; Stage #2: ethylene dibromide With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 4h;	226.226-A To a solution of pyridine (0.476 ml, 5.89 mmol) and p-anisidine (726 mg, 5.89 mmol) in acetonitrile (20 mL) was added a solution of ethyl (chlorosulfonyl)acetate (1.0 g, 5.36 mmol) in acetonitrile (30 mL) at 0°C. The reaction solution was stirred at the same temperature for 5 min, and at room temperature for 15 min. The reaction mixture was adjusted to pH≤2 by adding water and concentrated hydrochloric acid at 0°C, and the mixture was extracted with ethyl acetate. The organic layer was separated, washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. To a mixture of the obtained residue, potassium carbonate (1.49 g, 10.8 mmol) and DMF (40 mL) was added dropwise a solution of 1,2-dibromoethane (0.372 ml, 4.30 mmol) in DMF (40 mL) over 1.5 hr at 60°C and the mixture was stirred at the same temperature for 2.5 hr. The reaction mixture was cooled to room temperature, adjusted to pH≤2 with concentrated hydrochloric acid, and extracted with ethyl acetate. The organic layer was separated, washed with 0.1N hydrochloric acid and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography [eluent: hexane-ethyl acetate (17:3-3:2)] to give the title compound (438 mg) as a brown oil (yield 27%. 1H NMR (300 MHz, CDCl3) δ 1.35 (3H, t, J = 7.0 Hz), 2.52-2.68 (1H, m), 2.77-2.92 (1H, m), 3.61-3.73 (1H, m), 3.73-3.87 (4H, m), 4.18-4.27 (1H, m), 4.27-4.44 (2H, m), 6.84-6.96 (2H, m), 7.20-7.34 (2H, m).

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP2530078, 2012, A1 Location in patent: Page/Page column 198

59
[ 55896-93-0 ]
[ 452-84-6 ]
C₁₁H₁₄FNO₄S [ No CAS ]

Reference： [1]Molecules,2013,vol. 18,p. 2864 - 2877

60
[ 55896-93-0 ]
[ 371-40-4 ]
[ 1430475-71-0 ]

Yield	Reaction Conditions	Operation in experiment
79%	With triethylamine In dichloromethane at 20℃; for 3h; Inert atmosphere;
65%	With triethylamine In tetrahydrofuran at 0 - 20℃; for 1h; Inert atmosphere;	6.2 General methods for preparation of linear sulfonamide 3a-c General procedure: Sulfonyl chloride 1 (33mmol) in THF (10mL) was added dropwise to a solution of aromatic amine 2 (33mmol) and triethylamine (4.4mL, 35mmol) in 100mL THF at 0°C. Upon completion of the addition, the reaction mixture was stirred at room temperature for 1h before concentrated in vacuo. The residue was dissolved in EtOAc (100mL), washed with saturated brine (3×20mL), dried over Na2SO4, and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel to give compounds 3a-c.
	With triethylamine In dichloromethane at 0 - 20℃; for 16h;	Ethyl-2-[N-(4-fluorophenyl) sulfamoyl acetate (11a) Sodium -2-ethoxy-2-oxoethanesulfonate (40 g, 0.21 mol) & Phosphorous pentachloride (45.5 g, 0.22 mol) were mixed in a RB fitted with a reflux condenser. The reaction mixture was vigorously stirred magnetic stirrer for 15 min. The reaction mixture became exothermic & started refluxing. The reaction mixture was allowed to reflux for 2 h with external heating & cooled to RT. The reaction mixture was stripped off the POCl3 produced in the reaction mixture & added toluene and filtered. The filtrate obtained was added to a cooled mixture of Triethyl amine (42.6g, 0.42 mol) & 4-Fluoroaniline (27.5g, 0.23 mol) in DCM (200 mL). The reaction mixture was allowed to stir for 16 h at RT & added water (200 mL)and extracted with DCM. The DCM layer was washed with 1N HCl, followed by sat.aq bicarbonate solution, brine & dried over sodium sulfate. The DCM layer was concentrated under reduced pressure to get dark residue. Yield =65 %. 1HNMR (400 MHz, Chloroform-d6) δ 7.36 - 7.30 (m, 2H), 7.10 - 7.06 (m, 2H), 4.3 (q, 2H), 3.9 (s, 2H), 1.3 (t, 3H).LCMS (m+1) 261.8

Reference： [1]Reddy, M. V. Ramana; Mallireddigari, Muralidhar R.; Pallela, Venkat R.; Cosenza, Stephen C.; Billa, Vinay K.; Akula, Balaiah; Subbaiah, D. R. C. Venkata; Bharathi, E. Vijaya; Padgaonkar, Amol; Lv, Hua; Gallo, James M.; Reddy, E. Premkumar [Journal of Medicinal Chemistry, 2013, vol. 56, # 13, p. 5562 - 5586]
[2]Zhang, Wei; Ai, Jing; Shi, Dakuo; Peng, Xia; Ji, Yinchun; Liu, Jian; Geng, Meiyu; Li, Yingxia [European Journal of Medicinal Chemistry, 2014, vol. 80, p. 254 - 266]
[3]Chandrasekharappa, Arun P.; Badiger, Sangamesh E.; Dubey, Pramod K.; Panigrahi, Sunil K.; Manukonda, Sekhar Reddy V.V.V. [Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 9, p. 2579 - 2584]

61
[ 55896-93-0 ]
[ 14227-17-9 ]
[ 162519-52-0 ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 5562 - 5586

62
[ 55896-93-0 ]
[ 577-72-0 ]
[ 1445726-97-5 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of 3-nitro-4-methoxyaniline, 37 (107 mmol) in dichloromethane (150 mL) at 10 C, was added triethylamine (161 mmol) drop wise and stirred for 15 min at the same temperature. To this, ethyl 2-(chlorosulfonyl)acetate (22.0 g, 118 mmol) dissolved in dichloromethane (25 mL) was added slowly at the same temperature. Once the addition was over, the reaction mixture was allowed to warm to room temperature and stirred for 3 h. After completion of the reaction, water was added, and the reaction mixture was stirred for 15 min. The organic layer was separated, dried over anhydrous sodium sulfate and evaporated under reduced pressure to obtain crude 38. The crude 38 was purified on a silica gel column purification (1:1, ethyl acetate: hexane), resulting in pure 38 as a white crystalline sold, mp 115-119 C. 1H NMR (CDCl3, 300 MHz): delta 1.36 (t, J = 7.2 Hz, 3H, CH3), 3.94 (s, 2H, CH2), 3.99 (s, 3H, OCH3), 4.32 (q, J = 7.2 Hz, 2H, OCH2), 7.07 (br s, 1H, NH), 7.13 (d, J = 9.0 Hz, 1H, Ar-H), 7.62 (dd, J = 2.7, 9.0 Hz, 1H, Ar-H), 7.86 (d, J = 2.7 Hz, 1H, Ar-H).

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 5562 - 5586
[2]Patent: WO2017/23912,2017,A1 .Location in patent: Page/Page column 62; 63

63
[ 55896-93-0 ]
[ 16292-17-4 ]
[ 1581259-52-0 ]

Reference： [1]Chemical Communications,2014,vol. 50,p. 3616 - 3618

64
[ 55896-93-0 ]
[ 1205-71-6 ]
[ 1581259-56-4 ]

Reference： [1]Chemical Communications,2014,vol. 50,p. 3616 - 3618

65
[ 55896-93-0 ]
[ 6775-40-2 ]
ethyl 2-((4-phenyl-1H-imidazol-2-yl)sulfamoyl)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; triethylamine; In dichloromethane;	General procedure: To a solution of 4-aryl-1H-imidazol-2-amine (1) (0.477 g, 3.0 mmol) in dichloromethane(10 mL), triethylamine (3.1 mmol), and 4-dimethylaminopyridine (DMAP) (0.1 mmol) were added and stirred at room temperature for 15 min. Then, a solution of ethyl 2-chlorosulfonylacetate (0.615 g, 3.3 mmol) in dichloromethane(5 mL) was added dropwise and the reaction mixture was stirred at 40 C under nitrogen atmosphere for 6-10 h. After completion of reaction the solvent was removed in vacuo. The resultant residue was neutralized with saturated NaHCO3 solution and the aqueous layer was extracted with ethyl acetate, washed with water and dried over anhydrous Na2SO4. The solvent was removed under vacuum and the resultant solid was purified by column chromatography (silica gel, 60-120 mesh) using hexane-ethyl acetate (3:1) as eluent.

Reference： [1]Chemistry and biodiversity,2019,vol. 16
[2]Journal of Heterocyclic Chemistry,2014,vol. 51,p. 1875 - 1882
[3]Research on Chemical Intermediates,2015,vol. 41,p. 4413 - 4426

66
[ 55896-93-0 ]
[ 464-45-9 ]
ethyl (1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yloxysulfonylacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With pyridine In dichloromethane at 0℃; for 12h;	General procedure for preparation of sulfonates. General procedure: To the corresponding alcohol (1 mmol), dissolved in CH2Cl2 (5 ml) at 0°C, chlorosulfonyl acetic acid ethyl ester (1.5 mmol) was added, followed by pyridine (2 mmol). The reaction mixture was kept at 0 °C for 12 h. After warming up to room temperature, the reaction mixture was diluted with EtOAc (40 ml), washed with 1M HCl (30 ml), saturated NaHCO3, brine, and dried over anhydrous Na2SO4. The volatiles were removed under reduced pressure to yield the crude product that was purified on silica column (Ethyl Acetate-Hexanes, 0 to 50%) to yield the pure sulfonate.

Reference： [1]Liyanage, Duminda S.; Jungong, Christian S.; Novikov, Alexei V. [Synthetic Communications, 2015, vol. 45, # 2, p. 226 - 231]

67
[ 55896-93-0 ]
[ 23283-97-8 ]
ethyl (1S,2R,5R)-2-isopropyl-5-methylcyclohexan-1-yloxysulfonylacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With pyridine In dichloromethane at 0℃; for 12h;	General procedure for preparation of sulfonates. General procedure: To the corresponding alcohol (1 mmol), dissolved in CH2Cl2 (5 ml) at 0°C, chlorosulfonyl acetic acid ethyl ester (1.5 mmol) was added, followed by pyridine (2 mmol). The reaction mixture was kept at 0 °C for 12 h. After warming up to room temperature, the reaction mixture was diluted with EtOAc (40 ml), washed with 1M HCl (30 ml), saturated NaHCO3, brine, and dried over anhydrous Na2SO4. The volatiles were removed under reduced pressure to yield the crude product that was purified on silica column (Ethyl Acetate-Hexanes, 0 to 50%) to yield the pure sulfonate.

Reference： [1]Liyanage, Duminda S.; Jungong, Christian S.; Novikov, Alexei V. [Synthetic Communications, 2015, vol. 45, # 2, p. 226 - 231]

68
[ 70224-28-1 ]
[ 55896-93-0 ]
ethyl (R)-3-methylpentan-1-yloxysulfonylacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With pyridine In dichloromethane at 0℃; for 12h;	General procedure for preparation of sulfonates. General procedure: To the corresponding alcohol (1 mmol), dissolved in CH2Cl2 (5 ml) at 0°C, chlorosulfonyl acetic acid ethyl ester (1.5 mmol) was added, followed by pyridine (2 mmol). The reaction mixture was kept at 0 °C for 12 h. After warming up to room temperature, the reaction mixture was diluted with EtOAc (40 ml), washed with 1M HCl (30 ml), saturated NaHCO3, brine, and dried over anhydrous Na2SO4. The volatiles were removed under reduced pressure to yield the crude product that was purified on silica column (Ethyl Acetate-Hexanes, 0 to 50%) to yield the pure sulfonate.

Reference： [1]Liyanage, Duminda S.; Jungong, Christian S.; Novikov, Alexei V. [Synthetic Communications, 2015, vol. 45, # 2, p. 226 - 231]

69
[ 55896-93-0 ]
[ 103-49-1 ]
ethyl 2-(N,N-dibenzylsulfamoyl)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	In dichloromethane at 20℃; for 24h;	1 4.2. Preparation of sulfonamides 12a-m Secondary amine 11 (5 mmol) was dissolved in 10 mL of dry dichloromethane (DCM) in a 50-mL one-necked flask, then to the flask was slowly added a solution of ethyl chlorosulfonylacetate (0.467 g, 2.5 mmol) in 5 mL of DCM during 1 min. The resultant solution was stirred at room temperature for 24 h. After removal of the solvent, the mixture was directly subjected to column chromatography to recover the secondary amine and to obtain the desired product 12. 4.2.1. Ethyl 2-(N,N-dibenzylsulfamoyl)acetate (12a) Yellow oil, 1.65 g, 95% yield (10 mmol scale), Rf = 0.5 (silica gel plate, EA:PE = 1:5, v/v). 1H NMR (400 MHz, CDCl3) δ: 7.34-7.24 (m, 10H), 4.40 (s, 4H), 4.20 (q, J = 7.2 Hz, 2H), 3.83 (s, 2H), 1.26 (t, J = 7.2 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ: 163.3, 135.3, 128.7, 128.6, 128.0, 62.2, 57.6, 51.2, 14.0. IR (KBr, cm-1): 1740, 1342, 1150. HRMS (ESI) calcd for C18H22NO4S+ [M+H+] m/z: 348.1264, found 348.1271.

Reference： [1]Huang, Peipei; Yang, Zhanhui; Xu, Jiaxi [Tetrahedron, 2017, vol. 73, # 23, p. 3255 - 3265]

70
[ 55896-93-0 ]
[ 14309-92-3 ]
ethyl 2-[N-benzyl-N-(4-nitrophenyl)sulfamoyl]acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	In dichloromethane at 20℃; for 24h;	2 4.2. Preparation of sulfonamides 12a-m General procedure: Secondary amine 11 (5 mmol) was dissolved in 10 mL of dry dichloromethane (DCM) in a 50-mL one-necked flask, then to the flask was slowly added a solution of ethyl chlorosulfonylacetate (0.467 g, 2.5 mmol) in 5 mL of DCM during 1 min. The resultant solution was stirred at room temperature for 24 h. After removal of the solvent, the mixture was directly subjected to column chromatography to recover the secondary amine and to obtain the desired product 12.

Reference： [1]Huang, Peipei; Yang, Zhanhui; Xu, Jiaxi [Tetrahedron, 2017, vol. 73, # 23, p. 3255 - 3265]

71
[ 55896-93-0 ]
[ 768-52-5 ]
ethyl 2-(N-isopropyl-N-phenylsulfamoyl)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	In dichloromethane at 20℃; for 24h;	3 4.2. Preparation of sulfonamides 12a-m General procedure: Secondary amine 11 (5 mmol) was dissolved in 10 mL of dry dichloromethane (DCM) in a 50-mL one-necked flask, then to the flask was slowly added a solution of ethyl chlorosulfonylacetate (0.467 g, 2.5 mmol) in 5 mL of DCM during 1 min. The resultant solution was stirred at room temperature for 24 h. After removal of the solvent, the mixture was directly subjected to column chromatography to recover the secondary amine and to obtain the desired product 12.

Reference： [1]Huang, Peipei; Yang, Zhanhui; Xu, Jiaxi [Tetrahedron, 2017, vol. 73, # 23, p. 3255 - 3265]

72
[ 55896-93-0 ]
[ 100-61-8 ]
[ 87712-30-9 ]

Yield	Reaction Conditions	Operation in experiment
82%	In dichloromethane at 20℃; for 24h;	5 4.2. Preparation of sulfonamides 12a-m General procedure: Secondary amine 11 (5 mmol) was dissolved in 10 mL of dry dichloromethane (DCM) in a 50-mL one-necked flask, then to the flask was slowly added a solution of ethyl chlorosulfonylacetate (0.467 g, 2.5 mmol) in 5 mL of DCM during 1 min. The resultant solution was stirred at room temperature for 24 h. After removal of the solvent, the mixture was directly subjected to column chromatography to recover the secondary amine and to obtain the desired product 12.

Reference： [1]Huang, Peipei; Yang, Zhanhui; Xu, Jiaxi [Tetrahedron, 2017, vol. 73, # 23, p. 3255 - 3265]

73
[ 55896-93-0 ]
[ 2403-22-7 ]
ethyl 2-(N-benzyl-N-butylsulfamoyl)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	In dichloromethane at 20℃; for 24h;	6 4.2. Preparation of sulfonamides 12a-m General procedure: Secondary amine 11 (5 mmol) was dissolved in 10 mL of dry dichloromethane (DCM) in a 50-mL one-necked flask, then to the flask was slowly added a solution of ethyl chlorosulfonylacetate (0.467 g, 2.5 mmol) in 5 mL of DCM during 1 min. The resultant solution was stirred at room temperature for 24 h. After removal of the solvent, the mixture was directly subjected to column chromatography to recover the secondary amine and to obtain the desired product 12.

Reference： [1]Huang, Peipei; Yang, Zhanhui; Xu, Jiaxi [Tetrahedron, 2017, vol. 73, # 23, p. 3255 - 3265]

74
[ 55896-93-0 ]
[ 2032-33-9 ]
ethyl 2-(N-benzyl-N-propylsulfamoyl)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
29%	In dichloromethane; at 20℃; for 24h;	General procedure: Secondary amine 11 (5 mmol) was dissolved in 10 mL of dry dichloromethane (DCM) in a 50-mL one-necked flask, then to the flask was slowly added a solution of ethyl chlorosulfonylacetate (0.467 g, 2.5 mmol) in 5 mL of DCM during 1 min. The resultant solution was stirred at room temperature for 24 h. After removal of the solvent, the mixture was directly subjected to column chromatography to recover the secondary amine and to obtain the desired product 12.

Reference： [1]Tetrahedron,2017,vol. 73,p. 3255 - 3265

75
[ 55896-93-0 ]
[ 3647-71-0 ]
ethyl 2-[N-benzyl-N-phenethylsulfamoyl]acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	In dichloromethane at 20℃; for 24h;	8 4.2. Preparation of sulfonamides 12a-m General procedure: Secondary amine 11 (5 mmol) was dissolved in 10 mL of dry dichloromethane (DCM) in a 50-mL one-necked flask, then to the flask was slowly added a solution of ethyl chlorosulfonylacetate (0.467 g, 2.5 mmol) in 5 mL of DCM during 1 min. The resultant solution was stirred at room temperature for 24 h. After removal of the solvent, the mixture was directly subjected to column chromatography to recover the secondary amine and to obtain the desired product 12.

Reference： [1]Huang, Peipei; Yang, Zhanhui; Xu, Jiaxi [Tetrahedron, 2017, vol. 73, # 23, p. 3255 - 3265]

76
[ 635-46-1 ]
[ 55896-93-0 ]
ethyl 2-[(1,2,3,4-tetrahydroquinolin-1-yl)sulfonyl]acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	In dichloromethane at 20℃; for 24h;	11 4.2. Preparation of sulfonamides 12a-m General procedure: Secondary amine 11 (5 mmol) was dissolved in 10 mL of dry dichloromethane (DCM) in a 50-mL one-necked flask, then to the flask was slowly added a solution of ethyl chlorosulfonylacetate (0.467 g, 2.5 mmol) in 5 mL of DCM during 1 min. The resultant solution was stirred at room temperature for 24 h. After removal of the solvent, the mixture was directly subjected to column chromatography to recover the secondary amine and to obtain the desired product 12.

Reference： [1]Huang, Peipei; Yang, Zhanhui; Xu, Jiaxi [Tetrahedron, 2017, vol. 73, # 23, p. 3255 - 3265]

77
[ 496-15-1 ]
[ 55896-93-0 ]
ethyl 2-(indolin-1-ylsulfonyl)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	In dichloromethane at 20℃; for 24h;	12 4.2. Preparation of sulfonamides 12a-m General procedure: Secondary amine 11 (5 mmol) was dissolved in 10 mL of dry dichloromethane (DCM) in a 50-mL one-necked flask, then to the flask was slowly added a solution of ethyl chlorosulfonylacetate (0.467 g, 2.5 mmol) in 5 mL of DCM during 1 min. The resultant solution was stirred at room temperature for 24 h. After removal of the solvent, the mixture was directly subjected to column chromatography to recover the secondary amine and to obtain the desired product 12.

Reference： [1]Huang, Peipei; Yang, Zhanhui; Xu, Jiaxi [Tetrahedron, 2017, vol. 73, # 23, p. 3255 - 3265]

78
[ 91-21-4 ]
[ 55896-93-0 ]
ethyl 2-[(1,2,3,4-tetrahydroisoquinolin-2-yl)sulfonyl]acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	In dichloromethane at 20℃; for 24h;	13 4.2. Preparation of sulfonamides 12a-m General procedure: Secondary amine 11 (5 mmol) was dissolved in 10 mL of dry dichloromethane (DCM) in a 50-mL one-necked flask, then to the flask was slowly added a solution of ethyl chlorosulfonylacetate (0.467 g, 2.5 mmol) in 5 mL of DCM during 1 min. The resultant solution was stirred at room temperature for 24 h. After removal of the solvent, the mixture was directly subjected to column chromatography to recover the secondary amine and to obtain the desired product 12.

Reference： [1]Huang, Peipei; Yang, Zhanhui; Xu, Jiaxi [Tetrahedron, 2017, vol. 73, # 23, p. 3255 - 3265]

79
[ 55896-93-0 ]
[ 121004-44-2 ]
ethyl trans-2-methyl-3-(3-nitrophenyl)-1,2-thiazetidine-4-carboxylate 1,1-dioxide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With pyridine In tetrahydrofuran at 20℃; for 24h; diastereoselective reaction;	3.2. General Procedure for the Sulfa-Staudinger Cycloadditions of Sulfonyl Chlorides 1a,c and Imines 2 General procedure: To a solution of imine 2 (1 mmol) in dry THF (2 mL) was added a solution of sulfonyl chloride 1a(or 1c) (0.5 mmol) in dry THF (0.5 mL) for 0.5 min at room temperature. The mixture was then allowedto stand at room temperature for 24 h, followed by dilution with ether (10 mL), washing with brine(10 mL), and drying over Na2SO4. Filtrating off the desiccant and removing the solvents under vacuumgave rise to a residue, which subsequently was subjected to column chromatography on silica gelwith a mixture of petroleum ether (PE, 30-60 °C) and ethyl acetate (EA) as eluent to give the desired β-sultam products.For the reactions in entries 10-12 in Table 1, the following procedure was used. To a solution ofimine 2a or 2b or 2c (22 mg, 0.125 mmol) and pyridine (12 mg, 0.15 mmol) in dry THF (0.5 mL) wasadded a solution of sulfonyl chloride 1a (28 mg, 0.15 mmol) in dry THF (0.25 mL) for 0.5 min at roomtemperature. Then the mixture was allowed to stand at room temperature for 24 h, followed bydilution with ether (5 mL), and washing with brine (5 mL). Removing the solvents under vacuum gave rise to a residue, which subsequently was subjected to NMR analysis to determine the trans/cis ratios and yields.