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Chemical Structure| 681808-26-4 Chemical Structure| 681808-26-4

Structure of 681808-26-4

Chemical Structure| 681808-26-4

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Product Details of [ 681808-26-4 ]

CAS No. :681808-26-4
Formula : C8H15NO4S
M.W : 221.27
SMILES Code : O=C(OC(C)(C)C)NS(=O)(C1CC1)=O
MDL No. :MFCD16660018

Safety of [ 681808-26-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P264-P270-P301+P312-P330-P501

Application In Synthesis of [ 681808-26-4 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 681808-26-4 ]

[ 681808-26-4 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 154350-29-5 ]
  • [ 24424-99-5 ]
  • [ 681808-26-4 ]
YieldReaction ConditionsOperation in experiment
99% Stage lc:oI IBocHN-SI Io[0182] Cyclopropanesulfonamide (5.0 g, 41.26 mmol, 1.0 eq.), triethylamine (8.62 g, 61.90 mmol, 1.5 eq.) and dichloromethane (50 mL) were charged in a 100 mL round bottom flask. Di-te/t-butyldicarbonate (10.8 g, 49.52 mmol, 1.2 eq.) and N,N- dimethylaminopyridine (252 mg, 2.06 mmol, 0.05 eq.) were added portion wise and the reaction mixture stirred at ambient temperature for 48 hours. The solvent was removed in vacuo and the residue diluted with water (20 mL). The aqueous phase was acidified to pH = 1 with 1M hydrochloric acid, and extracted with ethyl acetate (3 x 100 mL). The organic extracts were combined, washed with water (100 mL) and brine (100 mL), dried over magnesium sulfate, filtered and the solvent removed in vacuo to give 9.1 g (99% yield) of the title compound as a white solid. 1H NMR (500 MHz, CDC13) δ ppm 7.14 (br. s., 1 H) 2.90 (tt, 7=8.09, 4.73 Hz, 1 H) 1.50 - 1.54 (m, 9 H) 1.35 - 1.40 (m, 2 H) 1.09 - 1.15 (m, 2 H). LC-MS: purity 100% (UV), tR 1.62 min m/z [M+Na]+ 243.95 (MET/CR/1278).
96% With dmap; triethylamine; In dichloromethane; at 20℃;Cooling with ice; To an iced slurry of <strong>[154350-29-5]cyclopropanesulfonamide</strong> (1.21 g, 9.99 mmol), Triethylamine (2.95 mL, 20.97 mmol), and 4-Dimethylaminopyridine (0.061 g, 0.499 mmol) in CH2Cl2 (50 mL) was added solution of Di-tert-butyl dicarbonate (2.423 mL, 10.99 mmol) in DCM (10 mL) dropwise. The formed solution was stirred at room temperature overnight, Removed the solvent in vacuo. The residual oil was taken up in EtOAc and washed with 1M HCl and brine. Dried over MgSO4, filtered, and concentrated. The residue was purified by Biotage column, eluted with gradient 5%50% acetone-hexane to yield the desired produce tert-butyl cyclopropylsulfonylcarbamate (2.17 g, 9.61 mmol, 96% yield) as a viscous oil, which solidified upon standing on bench. 1H NMR (400 MHz, CDCl3) ppm 1.11-1.13 (m, 2H) 1.37-1.39 9m, 2H) 1.53 (s, 9H), 2.89-2.92 (m, 1H) 7.00-7.05 (b, NH).
94% With dmap; triethylamine; In dichloromethane; at 20℃; Step 4:; To the solid <strong>[154350-29-5]cyclopropanesulfonamide</strong> 2d4 (1.51 g ; 12.46 mmol) was added insequence: di-t-butyl-dicarbonate (3.26 g ; 14.95 mmol) dissolved in anhydrousdichloromethane (15 ml_), triethylamine (2.6 ml; 18.65 mmol) anddimethylaminopyridine (76 mg; 0.622 mmol). The resulting solution was stirred atroom temperature overnight and subsequently evaporated to near dryness. Theresidue was diluted with EtOAc, washed with 1N aq. HCI (3x) and brine (1x), dried(MgSO4), filtered and evaporated to dryness to provide the Boc-<strong>[154350-29-5]cyclopropylsulfonamide</strong> product 2d5 as a white solid (2.6 g ; 94%).
94% With dmap; triethylamine; In dichloromethane; at 20℃; To the solid <strong>[154350-29-5]cyclopropanesulfonamide</strong> 2d4 (1.51 g; 12.46 mmol) was added in sequence: di-t-butyl-dicarbonate (3.26 g; 14.95 mmol) dissolved in anhydrous dichloromethane (15 mL), triethylamine (2.6 mL; 18.65 mmol) and dimethylaminopyridine (76 mg; 0.622 mmol). The resulting solution was stirred at room temperature overnight and subsequently evaporated to near dryness. The residue was diluted with EtOAc, washed with 1 N aq. HCl (3×) and brine (1×), dried (MgSO4), filtered and evaporated to dryness to provide the Boc-<strong>[154350-29-5]cyclopropylsulfonamide</strong> product 2d5 as a white solid (2.6 g; 94%).
94% With dmap; triethylamine; In dichloromethane; at 18 - 22℃; Step D; To the solid <strong>[154350-29-5]cyclopropanesulfonamide</strong> 4A4 (1.51 g ; 12.46 mmol) was added in sequence: di-t-butyl-dicarbonate (3.26 g ; 14.95 mmol) dissolved in anhydrous dichloromethane (15 mL), triethylamine (2.6 mL; 18.65 mmol) and dimethylaminopyridine (76 mg; 0.622 mmol). The resulting solution was stirred at room temperature overnight and subsequently evaporated to near dryness. The residue was diluted with EtOAc, washed with 1 N aq. HCI (3x) and brine (1x), dried EPO <DP n="44"/>(MgSO4), filtered and evaporated to dryness to provide the Boc- <strong>[154350-29-5]cyclopropylsulfonamide</strong> product 4A5 as a white solid (2.6 g ; 94%).
93% With dmap; triethylamine; In dichloromethane; for 5.08333h; Compound 2 (4g, 33 mmol) was suspended in dry DCM (100 mL) containing Et3N (5 mL, 36.3 mmol) and DMAP (0.4g , 3.3 mmol). A solution of (Boc)20 (8.3g, 38 mmol) in dry DCM (50 mL) was added dropwise with stirring over 5 min. after 5h, the solution was concentrated in vacuo and the residue treated with EtOAc (30OmL) and IN HCl. The EtOAc layer was washed successively with water (40 mLl) and brine (40 mL), dried (Na2SO4), and concentrated to leave a solid. Heating with hexane (30 mL), cooling to room temperature, and filtration provide compound 3 as a white solid 6.8 g (yield 93%).
88% With dmap; triethylamine; In dichloromethane; To a solution of <strong>[154350-29-5]cyclopropanesulfonamide</strong> (6 g, 50 mmol) in DCM (50 ml) were added triethylamine (7.5 ml, 74 mmol) followed by DMAP (0.3 g, 7.5 mmol) and di-tert-butyl dicarbonate (13 g, 59 ml) and the reaction was left stirring overnight. The solvent was removed; water, 2N HCl (40 ml) and ethyl acetate were added. The organic layer was washed with brine, dried over magnesium sulfate and evaporated to give Boc-<strong>[154350-29-5]cyclopropanesulfonamide</strong> as a white solid, used on the next step without further purification. Yield 9.73 g (88%).
87% With dmap; triethylamine; In dichloromethane; at 0 - 20℃; for 3.5h; Step 1: Preparation of Boc-cyclopropane sulfonyl amide 50. To a solution of <strong>[154350-29-5]cyclopropanesulfonamide</strong>, TEA (13.9 mL), and DMAP (1.11 g, 0.1 eq.) (10.72 g, leq.) in DCM (160 mL) was added a solution of BoC2O (21.88 g, 0.8 eq.) in DCM (10OmL) was added dropwise at 0 0C over 30 min. The mixture was then allowed to warm up to room temperature and stirred for 3 hrs. The solution was washed with IN HCl, water and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to yield after trituration in hexane compound 50 as a white solid in 87% yield.1H NMR (CDCl3, 400 MHz): δ 0.92-0.96 (td, J = 6.5 and 1.50 Hz, 2H), 1.51 (s, 9H), 1.60- 1.64 (td, 7 = 6.46 and 1.50 Hz, 2H), 1.25 (m, IH), 6.99 (brs, IH).
85% With dmap; triethylamine; In dichloromethane; at 20℃;Product distribution / selectivity; C.5) Alternative Preparation of Cyclopropylsulfonylamine tert-butyl carbamate To a solution of <strong>[154350-29-5]cyclopropylsulfonamide</strong> (6.0 g, 50.0 mmol) in CH2Cl2 (50 mL) was added BOC2O (13.0 g, 59.0 mmol), triethylamine (7.5 mL, 74 mmol), and 4-DMAP (0.30 g, 2.5 mmol). The reaction mixture was stirred overnight at room temperature, diluted with ethyl acetate (300 mL), partitioned with 1 N HCl (3*100 mL), dried over MgSO4, filtered, and concentrated in vacuo to provide 9.3 g (85%) of cyclopropylsulfonylamine tert-butylcarbamate.
85% With dmap; triethylamine; In dichloromethane; at 20℃;Product distribution / selectivity; Step ii) To a solution of <strong>[154350-29-5]cyclopropylsulfonamide</strong> (6.0 g, 50.0 mmol) in CH2Cl2 (50 mL) was added BOC2O(13.0 g, 59.0 mmol), Et3N (7.5 mL, 74 mmol), and 4-DMAP (0.30 g, 2.5 mmol). The reaction mixture was stirred overnite at rt, diluted with EtOAc (300 mL), partitioned with 1 N HCl (3*100 mL), dried over MgSO4 and concentrated in vacuo to afford 9.3 g (85%) of cyclopropylsulfonylamine tert-butylcarbamate as a white solid having identical data to its preparation in Step IIc.
With dmap; triethylamine; In dichloromethane; at 0 - 20℃; Step a: tert-butyl (cyciopropyisuifonyi)carbamate To a mixture of 15 g (124 mmof) cyclopropanβsulfo nic acid amide, 25.9 mL (186 mmol) triethylamine and 0.8 g (6.2 mmol) DMAP in 150 ml DCM was added 32.4 g (149 mmol) Boc- anhydride at OC. The mixture was slowly warmed to RT and stirred for 48 h. After dilution with DCM the mixture was washed with 1 N aq. HCi solution. The organic layer was dried over Na2SO4 and concentrated in vacuo to yield the title compound which was used in the next step without further purification. LC-MS (method E): Rt = 1.254 min; MIz = 220.2 [M-H].
2.66 g With dmap; triethylamine; In dichloromethane; for 16h; N-tert-Butyloxycarbonyl<strong>[154350-29-5]cyclopropanesulfonamide</strong> 1.46 g of <strong>[154350-29-5]cyclopropanesulfonamide</strong> were initially charged in a mixture of 30 ml of dichloromethane and 1.67 ml of triethylamine, and then 2.63 g of di-tert-butyl dicarbonate and 0.15 g of 4-dimethylaminopyridine were added and the mixture was stirred for 16 hours. The reaction solution was washed with 1 N aqueous hydrochloric acid, saturated aqueous sodium chloride solution and water, and the organic phase was dried over Na2SO4 and concentrated by rotary evaporation. This gave the product (2.66 g) with a molecular weight of 221.3 g/mol (C8H15NO4S); MS (ESI): m/e=166 (M-tert-Butyl+H+).
2.66 g With dmap; triethylamine; In dichloromethane; for 16h; N-tert-Butyloxycarbonyl<strong>[154350-29-5]cyclopropanesulfonamide</strong> 1.46 g of <strong>[154350-29-5]cyclopropanesulfonamide</strong> were initially charged in a mixture of 30 ml of dichloromethane and 1.67 ml of triethylamine, and then 2.63 g of di-tert-butyl dicarbonate and 0.15 g of 4-dimethylaminopyridine were added and the mixture was stirred for 16 hours. The reaction solution was washed with 1 N aqueous hydrochloric acid, saturated aqueous sodium chloride solution and water, and the organic phase was dried over Na2SO4 and concentrated by rotary evaporation. This gave the product (2.66 g) with a molecular weight of 221.3 g/mol (C8H15NO4S); MS (EST): m/e=166 (M-tert-Butyl+H+).
2.66 g With dmap; triethylamine; In dichloromethane; for 16h; 1.46 g of <strong>[154350-29-5]cyclopropanesulfonamide</strong> were initially charged in a mixture of 30 ml of dichloromethane and 1.67 ml of triethylamine, and then 2.63 g of di-tert-butyl dicarbonate and 0.15 g of 4-dimethylaminopyridine were added and the mixture was stirred for 16 hours. The reaction solution was washed with 1 N aqueous hydrochloric acid, saturated aqueous sodium chloride solution and water, and the organic phase was dried over Na2SO4 and concentrated by rotary evaporation. This gave the product (2.66 g) with a molecular weight of 221.3 g/mol (C8H15NO4S); MS (ESI): m/e=166 (M-tert-butyl+H+).
With dmap; triethylamine; In dichloromethane; at 0 - 25℃; Step 2: Preparation of tert-butyl cyclopropylsulfonylcarbamate: To a solution of A3 (2.0 g, 16.5 mmol) in DCM (30 mL) at 0 C was added DMAP (0.1 g, 0.825 mmol), Et3N (3.52 mL, 24.7 mmol) and Boc20 (4.32 g, 19.8 mmol). The reaction mixture was allowed to warm to RT and stir overnight. After that time, the volatiles were removed under reduced pressure. To the crude residue was added water. The aqueous phase was acidified to pH= 1 with the addition of aqueous 1.0 N HC1 and the mixture was extracted with EtOAc. The combined organic layers were washed with water and brine, then dried over Na2S04, filtered and concentrated to yield compound A4. NMR (CDC13, 300 MHz): δ 7.20 (bs, 1H), 2.92 - 2.86 (m, 1H), 1.55 (s, 9H), 1.39 - 1.35 (m, 2H), 1.28 - 1.24 (m, 2H).
With dmap; triethylamine; In dichloromethane; at 0 - 20℃; for 4h; To a solution of <strong>[154350-29-5]cyclopropanesulfonamide</strong> (100 g, 82.6 mmol) in DCM (800 ml) was added triethylamine (234 ml, 165 mmol) followed by DMAP (10.28 g, 82.6 mmol) at 0 C. under nitrogen. To this reaction mixture Boc anhydride (247 ml, 107 mmol) in DCM (400 ml) was added slowly. The resulting mixture was stirred for 4 h at room temperature. The reaction mixture was diluted with water and extracted with ethyl acetate. The combine organic layer was washed with 1.5 N HCl solution and 10% NaHCO3and dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to get crude compound (143 g, 65.0%) as solid. The crude compound was directly taken for the next step.1H NMR (400 MHz, DMSO-d6): δ ppm 11.08 (s, 1H), 2.90 (m, 1H), 1.48 (s, 9H), 1.06 (m, 4H).
With dmap; triethylamine; In dichloromethane; at 0 - 20℃; for 4h;Inert atmosphere; To a solution of <strong>[154350-29-5]cyclopropanesulfonamide</strong> (100 g, 82.6 mmol) in DCM (800 ml) was added triethylamine (234 ml, 165 mmol) followed by DMAP (10.28 g, 82.6 mmol) at 0 C. under nitrogen. To this reaction mixture Boc anhydride (247 ml, 107 mmol) in DCM (400 ml) was added slowly. The resulting mixture was stirred for 4 h at room temperature. The reaction mixture was diluted with water and extracted with ethyl acetate. The combine organic layer was washed with 1.5 N HCl solution and 10% NaHCO3 and dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to get crude compound (143 g, 65%) as a solid. The crude compound was directly taken for the next step. 1H NMR (400 MHz, DMSO-d6): δ ppm 11.08 (s, 1H), 2.90 (m, 1H), 1.48 (s, 9H), 1.06 (m, 4H).
65% (143 g) With dmap; triethylamine; In dichloromethane; at 0 - 20℃; for 4h; Step 1: Preparation of tert-butyl cyclopropylsulfonylcarbamate To a solution of <strong>[154350-29-5]cyclopropanesulfonamide</strong> (100 g, 82.6 mmol) in DCM (800 ml) was added triethylamine (234 ml, 165 mmol) followed by DMAP (10.28 g, 82.6 mmol) at 0 C. under nitrogen. To this reaction mixture Boc anhydride (247 ml, 107 mmol) in DCM (400 ml) was added slowly. The resulting mixture was stirred for 4 h at room temperature. The reaction mixture was diluted with water and extracted with ethyl acetate. The combine organic layer was washed with 1.5 N HCl solution and 10% NaHCO3 and dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to get crude compound (143 g, 65.0%) as solid. The crude compound was directly taken for the next step. 1H NMR (400 MHz, DMSO-d6): δ ppm 11.08 (s, 1H), 2.90 (m, 1H), 1.48 (s, 9H), 1.06 (m, 4H).
With dmap; triethylamine; In dichloromethane; at 0 - 20℃; for 12h; To a solution of <strong>[154350-29-5]cyclopropanesulfonamide</strong> (100 g, 825 mmol) in DCM (1 L) at 0 C was sequentially added DMAP (5.0 g, 41.3 mmol), TEA (173 mL, 1238 mmol), and Boc-anhydride (216 g, 813 mmol). The reaction mixture was allowed to warm to RT and stirred for 12 h. After the completion of reaction (monitored by TLC), it was concentrated under reduced pressure. The crude residue was taken in EtOAc (2000 mL) and washed with aqueous 1.5 _ HC1 (2 x 1000 mL). The organic layer was washed with water (1000 mL), brine (1000 mL) and dried over Na2SO4. The organic layer was concentrated under reduced pressure to afford 22a (180 g, 99%) as a transparent liquid, which was used in next step without purification. MS (ESI -ve ion) m/z: [M-1] = 220.2.1H NMR (400 MHz, chloroform-d) ^ 7.36 (s, 1H), 2.93- 2.88 (m, 1H), 1.53 (d, J = 0.6 Hz, 9H), 1.39-1.36 (m, 2H), 1.15-1.10 (m, 2H).

 

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