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[ CAS No. 669008-25-7 ]

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Chemical Structure| 669008-25-7
Chemical Structure| 669008-25-7
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CAS No. :669008-25-7 MDL No. :MFCD11707046
Formula : C8H17NO2S Boiling Point : 259°C at 760 mmHg
Linear Structure Formula :- InChI Key :-
M.W :191.29 g/mol Pubchem ID :21889792
Synonyms :

Safety of [ 669008-25-7 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 669008-25-7 ]

  • Upstream synthesis route of [ 669008-25-7 ]
  • Downstream synthetic route of [ 669008-25-7 ]

[ 669008-25-7 ] Synthesis Path-Upstream   1~4

  • 1
  • [ 669008-25-7 ]
  • [ 669008-26-8 ]
YieldReaction ConditionsOperation in experiment
96% at 20℃; for 16 h; Step 3: Preparation of 1-methylcyclopropylsulfonamide A solution of N-tert-butyl-(1-methyl)cyclopropylsulfonamide (1.91 g, 10 mmol) was dissolved in TFA (30 mL), and the reaction mixture stirred at room temperature for 16 hours. The solvent was removed in vacuo to give a yellow oil which was crystallized from ethyl acetate/hexane (1:4, 40 mL) to yield Example 3, 1-methylcyclopropylsulfonamide, as a white solid (1.25 g, 96percent): 1H NMR (CDCl3) δ 0.84 (m, 2H), 1.41 (m, 2H), 1.58 (s, 3H), 4.65 (br s, 2H). Anal. Calcd. For C4H9NO2S: C, 35.54; H, 6.71; N, 10.36. Found: C, 35.67; H, 6.80; N, 10.40.
96% at 20℃; for 16 h; A solution of N-tert-butyl-(1-methyl)cyclopropylsulfonamide (1.91 g, 10 mmol) (Step A.1.a) was dissolved in TFA (30 mL), and the reaction mixture stirred at room temperature for 16 hours. The solvent was removed in vacuo to give a yellow oil which was crystallized from ethyl acetate/hexane (1:4, 40 mL) to yield 1-methylcyclopropylsulfonamide as a white solid (1.25 g, 96percent): 1H NMR (CDCl3) δ 0.84 (m, 2H), 1.41 (m, 2H), 1.58 (s, 3H), 4.65 (br s, 2H). Anal. Calcd. For C4H9NO2S: C, 35.54; H, 6.71; N, 10.36. Found: C, 35.67; H, 6.80; N, 10.40.
96% at 20℃; for 16 h; A solution of N-tert-butyl-(1-methyl)cyclopropylsulfonamide (1.91 g, 10 mmol) was dissolved in TFA (30 mL), and the reaction mixture stirred at room temperature for 16 hours.
The solvent was removed in vacuo to provide a yellow oil which was crystallized from ethyl acetate/hexane (1:4, 40 mL) to provide the desired product as a white solid (1.25 g, 96percent): 1H NMR (CDCl3) δ 0.84 (m, 2H), 1.41 (m, 2H), 1.58 (s, 3H), 4.65 (br s, 2H). Anal. Calcd. For C4H9NO2S: C, 35.54; H, 6.71; N, 10.36. Found: C, 35.67; H, 6.80; N, 10.40.
96% at 20℃; for 16 h; A solution of N-tert-butyl-(1-methyl)cyclopropylsulfonamide (1.91 g, 10 mmol) was dissolved in TFA (30 mL), and the reaction mixture stirred at rt for 16 h. The solvent was removed in vacuo to give a yellow oil which was crystallized from EtOAc/hexane (1: 4, 40 mL) to yield 1-methylcyclopropylsulfonamide, as a white solid (1.25 g, 96percent): 1H NMR (CDCl3) δ 0.84 (m, 2H), 1.41 (m, 2H), 1.58 (s, 3H), 4.65 (bs, 2H). Anal. Calcd. For C4H9NO2S: C, 35.54; H, 6.71; N, 10.36. Found: C, 35.67; H, 6.80; N, 10.40.
96% at 20℃; for 16 h; A solution of N-tert-Butyl-(1-methyl)cyclopropylsulfonamide (1.91 g, 10 mmol) was dissolved in TFA (30 mL), and the reaction mixture stirred at rt for 16 h. The solvent was removed in vacuo to give a yellow oil which was crystallized from EtOAc/hexane (1:4, 40 mL) to yield Example 3, 1-methylcyclopropylsulfonamide, as a white solid (1.25 g, 96percent): 1H NMR (CDCl3) δ 0.84 (m, 2H), 1.41 (m, 2H), 1.58 (s, 3H), 4.65 (bs, 2H). Anal. Calcd. For C4H9NO2S: C, 35.54; H, 6.71; N, 10.36. Found: C, 35.67; H, 6.80; N, 10.40.
96% at 20℃; for 16 h; A solution of N-tert-Butyl-(l-methyl) cyclopropylsulfonamide (1.91 g, 10 mmol) was dissolved in TFA (30 mL), and the reaction mixture stirred at rt for 16 h. The solvent was removed in vacuo to give a yellow oil which was crystallized from EtOAc/ hexane (1 : 4,40 mL) to yield Example 3, 1-methylcyclopropylsulfonamide, as a white solid (1.25 g, 96percent) : 1H NMR (CDC13) 8 0.84 (m, 2H), 1.41 (m, 2H), 1.58 (s, 3H), 4.65 (bs, 2H). Anal. Calcd. For C4H9N02S : C, 35.54 ; H, 6.71 ; N, 10.36. Found: C, 35.67 ; H, 6.80 ; N, 10.40.
96% at 20℃; for 16 h; Step Ic: Preparation of 1-methylcyclopropylsulfonamide; A solution of N-tert-butyl-(l-methyl)cyclopropylsulfonamide (1.91 g, 10 mmol) was dissolved in TFA (30 mL), and the reaction mixture stirred at rt for 16 h. The solvent was removed in vacuo to give a yellow oil which was crystallized from EtOAc / hexane (1 : 4, 40 mL) to yield Example 3, 1-methylcyclopropylsulfonamide, as a white solid (1.25 g, 96percent): 1H νMR (CDCl3) δ 0.84 (m, 2H), 1.41 (m, 2H), 1.58 (s, 3H), 4.65 (bs, 2H). Anal. Calcd. For C4H9NO2S: C, 35.54; H, 6.71; N, 10.36. Found: C, 35.67; H, 6.80; N, 10.40.
96% at 20℃; for 16 h; A solution of N-tert-butyl-(1-methyl)cyclopropylsulfonamide (1.91 g, 10 mmol) was dissolved in TFA (30 mL), and the reaction mixture stirred at rt for 16 h.
The solvent was removed in vacuo to give a yellow oil which was crystallized from EtOAc/hexane (1:4, 40 mL) to yield Example 3, 1-methylcyclopropylsulfonamide, as a white solid (1.25 g, 96percent): 1H NMR (CDCl3) δ 0.84 (m, 2H), 1.41 (m, 2H), 1.58 (s, 3H), 4.65 (bs, 2H). Anal. Calcd. For C4H9NO2S: C, 35.54; H, 6.71; N, 10.36. Found: C, 35.67; H, 6.80; N, 10.40.
96% at 20℃; for 16 h; Step 1c:
Preparation of 1-methylcyclopropylsulfonamide
A solution of N-tert-butyl-(1-methyl)cyclopropylsulfonamide (1.91 g, 10 mmol) was dissolved in TFA (30 mL), and the reaction mixture stirred at rt for 16 h.
The solvent was removed in vacuo to give a yellow oil which was crystallized from EtOAc/hexane (1:4, 40 mL) to yield Example 3, 1-methylcyclopropylsulfonamide, as a white solid (1.25 g, 96percent): 1H NMR (CDCl3) δ 0.84 (m, 2H), 1.41 (m, 2H), 1.58 (s, 3H), 4.65 (bs, 2H). Anal. Calcd. For C4H9NO2S: C, 35.54; H, 6.71; N, 10.36. Found: C, 35.67; H, 6.80; N, 10.40.
96% at 20℃; for 16 h; A solution of N-tert-butyl-(1-methyl)cyclopropylsulfonamide (1.91 g, 10 mmol) was dissolved in TFA (30 mL), and the reaction mixture stirred at rt for 16 h. The solvent was removed in vacuo to give a yellow oil which was crystallized from EtOAc/hexane (1:4, 40 mL) to yield 1-methylcyclopropylsulfonamide, as a white solid (1.25 g, 96percent): 1H NMR (CDCl3) δ 0.84 (m, 2H), 1.41 (m, 2H), 1.58 (s, 3H), 4.65 (bs, 2H). Anal. Calcd. For C4H9NO2S: C, 35.54; H, 6.71; N, 10.36. Found: C, 35.67; H, 6.80; N, 10.40.
96% at 20℃; for 16 h; A solution of N-tert-butyl-(1-methyl)cyclopropylsulfonamide (1.91 g, 10 mmol) was dissolved in TFA (30 mL), and the reaction mixture stirred at rt for 16 h. The solvent was removed in vacuo to give a yellow oil which was crystallized from EtOAc/hexane (1:4, 40 mL) to yield 1-methylcyclopropylsulfonamide, as a white solid (1.25 g, 96percent): 1H NMR (CDCl3) δ 0.84 (m, 2H), 1.41 (m, 2H), 1.58 (s, 3H), 4.65 (bs, 2H). Anal. Calcd. For C4H9NO2S: C, 35.54; H, 6.71; N, 10.36. Found: C, 35.67; H, 6.80; N, 10.40
96% at 20℃; for 16 h; Step 3:
Preparation of 1-methylcyclopropylsulfonamide
A solution of the product of Step 2 (1.91 g, 10 mmol) was dissolved in TFA (30 mL), and the reaction mixture stirred at room temperature for 16 hours.
The solvent was removed in vacuo to provide a yellow oil which was crystallized from ethyl acetate/hexane (1:4, 40 mL) to provide the desired product as a white solid (1.25 g, 96percent): 1H NMR (CDCl3) δ 0.84 (m, 2H), 1.41 (m, 2H), 1.58 (s, 3H), 4.65 (br s, 2H). Anal. Calcd. For C4H9NO2S: C, 35.54; H, 6.71; N, 10.36. Found: C, 35.67; H, 6.80; N, 10.40.
96% at 20℃; for 16 h; A solution of N-tert-butyl-(l-methyl)cyclopropylsulfonamide (1.91 g, 10 mmol) was dissolved in TFA (30 mL), and the reaction mixture stirred at rt for 16 h. The solvent was removed in vacuo to give a yellow oil which was crystallized from EtOAc / hexane (1 : 4, 40 mL) to yield Example 3, 1-methylcyclopropylsulfonamide, as a white solid (1.25 g, 96percent): 1H νMR (CDCl3) δ 0.84 (m, 2H), 1.41 (m, 2H), 1.58 (s, 3H), 4.65 (bs, 2H). Anal. Calcd. For C4H9NO2S: C, 35.54; H, 6.71; N, 10.36. Found: C, 35.67; H, 6.80; N, 10.40.
56% at 20℃; Preparation 171-methylcyclopropane-1-sulfonamide[0074]N-(tert-butyl)-1-methylcyclopropane-1-sulfonamide (78.6 g, 411 mmol) and TFA (340 mL). The brown solution was stirred overnight at rt. The reaction mixture was concentrated (at 50° C.) to a brown oil. A stream of N2 was blown into the oil for about 35 minutes at the end of which a brown semi-solid formed. The semi-solid was suspended in ethyl acetate (80 mL) and hexane (231 mL). The suspension was stirred at rt for 10 minutes then vacuum filtered. The filter cake was rinsed with hexane then dried overnight to give a crude tan solid (51.6 g). The solid was recrystallized from a mixture of ethyl acetate (190 mL) and hexane (270 mL), (heat to reflux, cooled to rt and vacuum filtered at rt) to give an off white solid (37.6 g, 68percent yield). The off white solid (37.6 g) was dissolved in hot ethyl acetate (257 mL), diluted with hexane (177 mL) then refluxed for 5 minutes. The hot solution was cooled to rt, the resulting white suspension was vacuum filtered, and the filter cake was dried to a white solid (56.6 g, 416 mmol, 56percent yield). 1H NMR (500 MHz, DMSO-d6) δ 6.72 (bs, 2H), 1.44 (s, 3H), 1.13 (dd, J=6.1 and 4.0 Hz, 2H), 0.74 (dd, J=6.1 and 4.0 Hz, 2H). 13C NMR (125 MHz, DMSO-d6) δ 36.4, 17.6, 12.1.
56% at 20℃; Preparation 17: 1-methylcyclopropane-1-sulfonamide [0106] N-(tert-butyl)-1-methylcyclopropane-1 -sulfonamide (78.6 g, 411 mmol) and TFA (340 mL). The brown solution was stirred overnight at rt. The reaction mixture was concentrated (at 50 °C) to a brown oil. A stream of 2 was blown into the oil for about 35 minutes at the end of which a brown semi-solid formed. The semi-solid was suspended in ethyl acetate (80 mL) and hexane (231 mL). The suspension was stirred at rt for 10 minutes then vacuum filtered. The filter cake was rinsed with hexane then dried overnight to give a crude tan solid (51.6g). The solid was recrystallized from a mixture of ethyl acetate (190 mL) and hexane (270 mL), (heat to reflux, cooled to rt and vacuum filtered at rt) to give an off white solid (37.6 g, 68percent yield). The off white solid (37.6 g) was dissolved in hot ethyl acetate (257 mL), diluted with hexane (177 mL) then refluxed for 5 minutes. The hot solution was cooled to rt, the resulting white suspension was vacuum filtered, and the filter cake was dried to a white solid (56.6 g, 416 mmol, 56percent yield). 1H NMR (500 MHz, DMSO-d6) δ 6.72 (bs, 2 H), 1.44 (s, 3 H), 1.13 (dd, J= 6.1 and 4.0 Hz, 2 H), 0.74 (dd, J= 6.1 and 4.0 Hz, 2 H). 13C NMR (125 MHz, DMSO-d6) 5 36.4, 17.6, 12.1.

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  • 2
  • [ 63132-85-4 ]
  • [ 74-88-4 ]
  • [ 669008-25-7 ]
YieldReaction ConditionsOperation in experiment
99%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -69 - 20℃; for 4.33333 h;
Stage #2: at -65 - 50℃; for 4.66667 h;
Preparation 16N-(tert-butyl)-1-methylcyclopropane-1-sulfonamide[0072]N-(tert-butyl)-3-chloropropane-1-sulfonamide (Previously dried by azeotroping with 3×100 mL toluene) (100 g, 468 mmol) and THF (1500 mL). This was cooled to an internal temperature of −69° C. then butyl lithium (2.5M in hexanes, 412 mL, 1.02 mol) was added dropwise over a period of 55 min while keeping the internal temperature below −65° C. The ice bath was removed and the reaction mixture was warmed to rt over 1.5 h and then cooled back down to an internal temperature of −69° C. Butyl lithium (196 mL, 515 mmol) was added to the reaction mixture over a period of 25 min while keeping the internal temperature below −65° C. The reaction mixture was then warmed to rt over the course of 1.5 h. The reaction mixture was recooled to an internal temperature of −69° C. and iodomethane (58.5 mL, 936 mmol) was added dropwise over a period of 40 min while keeping the internal temperature below −65° C. The reaction mixture was then warmed to an internal temperature of −50° C. over the course of 4 h. The cold bath was removed and a solution of saturated NH4Cl (1000 mL) was added. The quenched reaction mixture was transferred to a separatory funnel along with ethyl acetate (100 mL) and water (500 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate. (3×75 mL). The combined organic layers were washed with brine (700 mL), dried with MgSO4, and concentrated in vacuo to an off white solid which was dried under high vac for 30 min to yield N-(tert-butyl)-1-methylcyclopropane-1-sulfonamide as a white solid (88.5 g, 99percent yield). 1H NMR (500 MHz, CDCl3) δ 4.07 (bs, 1H), 1.51 (s, 3H), 1.38-1.41 (m, 2H), 1.36 (s, 9H), 0.77-0.80 (m, 2H).
99%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -69 - 20℃; for 4.33333 h;
Stage #2: at -69 - -50℃; for 4.66667 h;
Preparation 16 N-(tert-butyl)-1-methylcyclopropane-1-sulfonamide [0104] N-(tert-butyl)-3-chloropropane-1-sulfonamide (Previously dried by azeotroping with 3 x 1OOmL toluene) (100 g, 468 mmol) and THF (1500 niL). This was cooled to an internal temperature of -69 °C then butyl lithium (2.5M in hexanes, 412 mL, 1.02 mol) was added dropwise over a period of 55 min while keeping the internal temperature below -65 °C. The ice bath was removed and the reaction mixture was warmed to rt over 1.5 h and then cooled back down to an internal temperature of -69 °C. Butyl lithium (196 mL, 515 mmol) was added to the reaction mixture over a period of 25 min while keeping the internal temperature below -65 °C. The reaction mixture was then warmed to rt over the course of 1.5h. The reaction mixture was recooled to an internal temperature of -69 °C and iodo methane (58.5 mL, 936 mmol) was added dropwise over a period of 40 min while keeping the internal temperature below-65 °C. The reaction mixture was then warmed to an internal temperature of -50 °C over the course of 4h. The cold bath was removed and a solution of saturated NH4C1 (1000 mL) was added. The quenched reaction mixture was transferred to a separatory funnel along with ethyl acetate (100 mL) and water (500 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate. (3 x 75 mL). The combined organic layers were washed with brine (700 mL), dried with MgS04, and concentrated in vacuo to an off white solid which was dried under high vac for 30 min to yield N-(tert-butyl)-1-methylcyclopropane-1 -sulfonamide as a white solid (88.5 g, 99percent yield). NMR (500 MHz, CDC13) δ 4.07 (bs, 1 H), 1.51 (s, 3 H), 1.38-1.41 (m, 2 H), 1.36 (s, 9 H), 0.77-0.80 (m, 2 H).
81%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; for 3.5 h;
Stage #2: at 20℃; Neat (no solvent)
A solution of N-tert-butyl-(3-chloro)propylsulfonamide (4.3 g, 20 mmol) was dissolved in dry THF (100 mL) and cooled to -78° C. To this solution was added n-BuLi (17.6 mL, 44 mmol, 2.5 M in hexane) slowly. The dry ice bath was removed and the reaction mixture was allowed to warm to rt over a period of 1.5 h. This mixture was then cooled to -78° C., and a solution of n-BuLi (20 mmol, 8 mL, 2.5 M in hexane) was added. The reaction mixture was warmed to rt, recooled to -78° C. over a period of 2 h and a neat solution of methyl iodide (5.68 g, 40 mmol) added. The reaction mixture was allowed to warm to rt overnight, quenched with saturated NH4Cl (100 mL) at rt. It was extracted with EtOAc (100 mL). The organic phase was washed with brine (100 mL), dried (MgSO4), and concentrated in vacuo to give a yellow oil which was crystallized from hexane to afford the product as a slightly yellow solid (3.1 g, 81percent): 1H NMR (CDCl3) δ 0.79 (m, 2H), 1.36 (s, 9H), 1.52 (m, 2H), 1.62 (s, 3H), 4.10 (bs, 1H).
81%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; for 3.5 h;
Stage #2: at -78 - 20℃;
A solution of N-tert-Butyl-(3-chloro)propylsulfonamide (4.3 g, 20 mmol) was dissolved in dry THF (100 mL) and cooled to -78° C. To this solution was added n-BuLi (17.6 mL, 44 mmol, 2.5 M in hexane) slowly. The dry ice bath was removed and the reaction mixture was allowed to warm to rt over a period of 1.5 h. This mixture was then cooled to -78° C., and a solution of n-BuLi (20 mmol, 8 mL, 2.5 M in hexane) was added. The reaction mixture was warmed to rt, recooled to -78° C. over a period of 2 h and a neat solution of methyliodide (5.68 g, 40 mmol) added. The reaction mixture was allowed to warm to rt overnight, quenched with saturated NH4Cl (100 mL) at rt. It was extracted with EtOAc (100 mL). The organic phase was washed with brine (100 mL), dried (MgSO4), and concentrated in vacuo to give a yellow oil which was crystallized from hexane to afford the product as a slightly yellow solid (3.1 g, 81percent): 1H NMR (CDCl3) δ 0.79 (m, 2H), 1.36 (s, 9H), 1.52 (m, 2H), 1.62 (s, 3H), 4.10 (bs, 1 H)
81%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; for 3.5 h;
Stage #2: at 20℃;
Stage #3: With ammonium chloride In tetrahydrofuran; hexane; water at 20℃;
A solution of N-tert-Butyl- (3-chloro) propylsulfonamide (4.3 g, 20 mmol) was dissolved in dry THF (100 mL) and cooled to-78 °C. To this solution was added n- BuLi (17.6 mL, 44 mmol, 2.5 M in hexane) slowly. The dry ice bath was removed and the reaction mixture was allowed to warm to rt over a period of 1.5 h. This mixture was then cooled to-78°C, and a solution of n-BuLi (20 mmol, 8 mL, 2.5 M in hexane) was added. The reaction mixture was warmed to rt, recooled to-78 °C over a period of 2 h and a neat solution of methyliodide (5.68 g, 40 mmol) added. The reaction mixture was allowed to warm to rt overnight, quenched with saturated NH4Cl (100 mL) at rt. It was extracted with EtOAc (100 mL). The organic phase was washed with brine (100 mL), dried (MgS04), and concentrated in vacuo to give a yellow oil which was crystallized from hexane to afford the product as a slightly yellow solid (3.1 g, 81percent) :'H NMR (CDCl3) 8 0.79 (m, 2H), 1.36 (s, 9H), 1.52 (m, 2H), 1.62 (s, 3H), 4.10 (bs, 1H)
81%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; for 3.5 h;
Stage #2: at -78 - 20℃;
Stage #3: With water; ammonium chloride In tetrahydrofuran; hexane at 20℃;
Step Ib. Preparation ofN-tert-Butyl-(l-methyl)cyclopropylsulfonamide.; A solution of N-tert-butyl-(3-chloro)propylsulfonamide (4.3 g, 20 mmol) was dissolved in dry THF (100 mL) and cooled to - 78 0C. To this solution was added n- BuLi (17.6 mL, 44 mmol, 2.5 M in hexane) slowly. The dry ice bath was removed and the reaction mixture was allowed to warm to rt over a period of 1.5h. This mixture was then cooled to - 78°C, and a solution of M-BuLi (20 mmol, 8 mL, 2.5 M in hexane) was added. The reaction mixture was warmed to rt, recooled to -78 0C over a period of 2 h and a neat solution of methyl iodide (5.68 g, 40 mmol) added. The reaction mixture was allowed to warm to rt overnight, quenched with saturated <n="54"/>NH4Cl (100 mL) at rt. It was extracted with EtOAc (100 mL). The organic phase was washed with brine (100 mL), dried (MgSO4), and concentrated in vacuo to give a yellow oil which was crystallized from hexane to afford the product as a slightly yellow solid (3.1 g, 81percent): 1H NMR (CDCl3) δ 0.79 (m, 2H), 1.36 (s, 9H), 1.52 (m, 2H), 1.62 (s, 3H), 4.10 (bs, IH).
81%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; for 3.5 h;
Stage #2: at -78 - 20℃;
A solution of N-tert-butyl-(3-chloro)propylsulfonamide (4.3 g, 20 mmol) was dissolved in dry THF (100 mL) and cooled to -78° C. To this solution was added n-BuLi (17.6 mL, 44 mmol, 2.5 M in hexane) slowly. The dry ice bath was removed and the reaction mixture was allowed to warm to rt over a period of 1.5 h. This mixture was then cooled to -78° C., and a solution of n-BuLi (20 mmol, 8 mL, 2.5 M in hexane) was added. The reaction mixture was warmed to rt, recooled to -78° C. over a period of 2 h and a neat solution of methyl iodide (5.68 g, 40 mmol) added. The reaction mixture was allowed to warm to rt overnight, quenched with saturated NH4Cl (100 mL) at rt. It was extracted with EtOAc (100 mL). The organic phase was washed with brine (100 mL), dried (MgSO4), and concentrated in vacuo to give a yellow oil which was crystallized from hexane to afford the product as a slightly yellow solid (3.1 g, 81percent): 1H NMR (CDCl3) δ 0.79 (m, 2H), 1.36 (s, 9H), 1.52 (m, 2H), 1.62 (s, 3H), 4.10 (bs, 1H).
81%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; for 3.5 h;
Stage #2: at -78 - 20℃;
A solution of N-tert-butyl-(3-chloro)propylsulfonamide (4.3 g, 20 mmol) was dissolved in dry THF (100 mL) and cooled to -78° C. To this solution was added n-BuLi (17.6 mL, 44 mmol, 2.5 M in hexane) slowly. The dry ice bath was removed and the reaction mixture was allowed to warm to rt over a period of 1.5 h. This mixture was then cooled to -78° C., and a solution of n-BuLi (20 mmol, 8 mL, 2.5 M in hexane) was added. The reaction mixture was warmed to rt, recooled to -78° C. over a period of 2 h and a neat solution of methyl iodide (5.68 g, 40 mmol) added. The reaction mixture was allowed to warm to rt overnight, quenched with saturated NH4Cl (100 mL) at rt. It was extracted with EtOAc (100 mL). The organic phase was washed with brine (100 mL), dried (MgSO4), and concentrated in vacuo to give a yellow oil which was crystallized from hexane to afford the product as a slightly yellow solid (3.1 g, 81percent): 1H NMR (CDCl3) δ 0.79 (m, 2H), 1.36 (s, 9H), 1.52 (m, 2H), 1.62 (s, 3H), 4.10 (bs, 1H).
81%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; for 3.5 h;
Stage #2: at 20℃;
A solution of N-tert-butyl-(3-chloro)propylsulfonamide (4.3 g, 20 mmol) was dissolved in dry THF (100 mL) and cooled to -78° C. To this solution was added n-BuLi (17.6 mL, 44 mmol, 2.5 M in hexane) slowly. The dry ice bath was removed and the reaction mixture was allowed to warm to rt over a period of 1.5 h. This mixture was then cooled to -78° C., and a solution of n-BuLi (20 mmol, 8 mL, 2.5 M in hexane) was added. The reaction mixture was warmed to rt, recooled to -78° C. over a period of 2 h and a neat solution of methyl iodide (5.68 g, 40 mmol) added. The reaction mixture was allowed to warm to rt overnight, quenched with saturated NH4Cl (100 mL) at rt. It was extracted with EtOAc (100 mL). The organic phase was washed with brine (100 mL), dried (MgSO4), and concentrated in vacuo to give a yellow oil which was crystallized from hexane to afford the product as a slightly yellow solid (3.1 g, 81percent): 1H NMR (CDCl3) δ 0.79 (m, 2H), 1.36 (s, 9H), 1.52 (m, 2H), 1.62 (s, 3H), 4.10 (bs, 1H).
81%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; for 2.5 h;
Stage #2: at 20℃; Neat (no solvent)
A solution of N-tert-butyl-(3-chloro)propylsulfonamide (4.3 g, 20 mmol) was dissolved in dry THF (100 mL) and cooled to -78° C. To this solution was added n-BuLi (17.6 mL, 44 mmol, 2.5 M in hexane) slowly. The dry ice bath was removed and the reaction mixture was allowed to warm to rt over a period of 1.5 h. This mixture was then cooled to -78° C., and a solution of n-BuLi (20 mmol, 8 mL, 2.5 M in hexane) was added. The reaction mixture was warmed to rt, recooled to -78° C. over a period of 2 h and a neat solution of methyl iodide (5.68 g, 40 mmol) added. The reaction mixture was allowed to warm to rt overnight, quenched with saturated NH4Cl (100 mL) at rt. It was extracted with EtOAc (100 mL). The organic phase was washed with brine (100 mL), dried (MgSO4), and concentrated in vacuo to give a yellow oil which was crystallized from hexane to afford the product as a slightly yellow solid (3.1 g, 81percent): 1H NMR (CDCl3) δ 0.79 (m, 2H), 1.36 (s, 9H), 1.52 (m, 2H), 1.62 (s, 3H), 4.10 (bs, 1H).
81%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃;
Stage #2: at -78 - 20℃;
Step 2: Preparation of N-tert-butyl-(1-methyl)cyclopropyl-sulfonamide A solution of the product of Step 1 (4.3 g, 20 mmol) was dissolved in dry THF (100 mL) and cooled to -78° C. To this solution was added n-butyllithium (17.6 mL, 44 mmol, 2.5M in hexane) slowly. The dry ice bath was removed and the reaction mixture was warmed to room temperature over a period of 1.5 hours. This mixture was cooled to -78° C. and a solution of n-butyllithium (20 mmol, 8 mL, 2.5M in hexane) was added. The reaction mixture was warmed to room temperature, cooled to -78° C. over a period of 2 hours, and treated with a neat solution of methyl iodide (5.68 g, 40 mmol). The reaction mixture was warmed to room temperature overnight, then quenched with saturated NH4Cl (100 mL) at room temperature and extracted with ethyl acetate (100 mL). The organic phase was washed with brine (100 mL), dried (MgSO4), filtered, and concentrated in vacuo to provide a yellow oil which was crystallized from hexane to provide the desired product as a slightly yellow solid (3.1 g, 81percent): 1H NMR (CDCl3) δ 0.79 (m, 2H), 1.36 (s, 9H), 1.52 (m, 2H), 1.62 (s, 3H), 4.10 (br s, 1H).
81%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; for 3.5 h; Cooling with dry ice
Stage #2: at -78 - 20℃;
A solution of N-tert-butyl-(3-chloro)propylsulfonamide (4.3 g, 20 mmol) was dissolved in dry THF (100 mL) and cooled to - 78 0C. To this solution was added n- <n="52"/>BuLi (17.6 mL, 44 mmol, 2.5 M in hexane) slowly. The dry ice bath was removed and the reaction mixture was allowed to warm to rt over a period of 1.5h. This mixture was then cooled to - 78°C, and a solution of M-BuLi (20 mmol, 8 mL, 2.5 M in hexane) was added. The reaction mixture was warmed to rt, recooled to -78 0C over a period of 2 h and a neat solution of methyl iodide (5.68 g, 40 mmol) added. The reaction mixture was allowed to warm to rt overnight, quenched with saturated NH4Cl (100 mL) at rt. It was extracted with EtOAc (100 mL). The organic phase was washed with brine (100 mL), dried (MgSO4), and concentrated in vacuo to give a yellow oil which was crystallized from hexane to afford the product as a slightly yellow solid (3.1 g, 81percent): 1H NMR (CDCl3) δ 0.79 (m, 2H), 1.36 (s, 9H), 1.52 (m, 2H), 1.62 (s, 3H), 4.10 (bs, IH).

Reference: [1] Patent: US2013/102589, 2013, A1, . Location in patent: Paragraph 0072; 0073
[2] Patent: EP2792360, 2014, A1, . Location in patent: Paragraph 0104-0105
[3] Synlett, 2006, # 5, p. 725 - 728
[4] Patent: US2008/107625, 2008, A1, . Location in patent: Page/Page column 25
[5] Patent: US2004/77551, 2004, A1, . Location in patent: Page/Page column 25
[6] Patent: WO2005/51410, 2005, A1, . Location in patent: Page/Page column 81
[7] Patent: WO2008/64061, 2008, A1, . Location in patent: Page/Page column 52-53
[8] Patent: US2007/93414, 2007, A1, . Location in patent: Page/Page column 40
[9] Patent: US2007/99825, 2007, A1, . Location in patent: Page/Page column 29
[10] Patent: US2008/107623, 2008, A1, . Location in patent: Page/Page column 24-25
[11] Patent: US2008/107624, 2008, A1, . Location in patent: Page/Page column 25
[12] Patent: US2008/119461, 2008, A1, . Location in patent: Page/Page column 24
[13] Patent: WO2008/64057, 2008, A1, . Location in patent: Page/Page column 50-51
[14] Patent: US2004/48802, 2004, A1,
  • 3
  • [ 74-88-4 ]
  • [ 669008-25-7 ]
YieldReaction ConditionsOperation in experiment
81%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; for 1.5 h;
Stage #2: With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; for 2 h;
Step 2: Preparation of N-tert-butyl-(1-methyl)cyclopropyl-sulfonamide A solution of N-tert-butyl-(3-chloro)propylsulfonamide (4.3 g, 20 mmol) was dissolved in dry THF (100 mL) and cooled to -78° C. To this solution was added n-butyllithium (17.6 mL, 44 mmol, 2.5M in hexane) slowly. The dry ice bath was removed and the reaction mixture was allowed to warm to room temperature over a period of 1.5 hours. This mixture was then cooled to -78° C., and a solution of n-butyllithium (20 mmol, 8 mL, 2.5M in hexane) was added. The reaction mixture was warmed to room temperature, re-cooled to -78° C. over a period of 2 hours and a neat solution of methyl iodide (5.68 g, 40 mmol) was added. The reaction mixture was allowed to warm to room temperature overnight, then quenched with saturated NH4Cl (100 mL) at room temperature. It was extracted with ethyl acetate (100 mL). The organic phase was washed with brine (100 mL), dried (MgSO4), filtered, and concentrated in vacuo to give a yellow oil which was crystallized from hexane to afford the product as a slightly yellow solid (3.1 g, 81percent): 1H NMR (CDCl3) δ 0.79 (m, 2H), 1.36 (s, 9H), 1.52 (m, 2H), 1.62 (s, 3H), 4.10 (br s, 1H).
81%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; for 3.5 h;
Stage #2: at 20℃;
A solution of N-tert-butyl-(3-chloro)propylsulfonamide (4.3 g, 20 mmol) was dissolved in dry THF (100 mL) and cooled to -78° C. To this solution was added n-BuLi (17.6 mL, 44 mmol, 2.5 M in hexane) slowly. The dry ice bath was removed and the reaction mixture was allowed to warm to room temperature over a period of 1.5 hours. This mixture was then cooled to -78° C., and a solution of n-BuLi (20 mmol, 8 mL, 2.5 M in hexane) was added. The reaction mixture was warmed to room temperature, recooled to -78° C. over a period of 2 hours and a neat solution of methyl iodide (5.68 g, 40 mmol) added. The reaction mixture was allowed to warm to room temperature overnight, quenched with saturated NH4Cl (100 mL) at room temperature. It was extracted with ethyl acetate (100 mL). The organic phase was washed with brine (100 mL), dried (MgSO4), filtered, and concentrated in vacuo to give a yellow oil which was crystallized from hexane to provide the product as a slightly yellow solid (3.1 g, 81percent): 1H NMR (CDCl3) δ 0.79 (m, 2H), 1.36 (s, 9H), 1.52 (m, 2H), 1.62 (s, 3H), 4.10 (br s, 1H).
81%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; for 8.5 h;
Stage #2: at 20℃;
A solution of N-tert-butyl-(3-chloro)propylsulfonamide (4.3 g, 20 mmol) was dissolved in dry THF (100 mL) and cooled to -78° C.
To this solution was added n-butyllithium (17.6 mL, 44 mmol, 2.5M in hexane) slowly.
The dry ice bath was removed and the reaction mixture was warmed to room temperature over a period of 1.5 hours.
This mixture was cooled to -78° C. and a solution of n-butyllithium (20 mmol, 8 mL, 2.5M in hexane) was added.
The reaction mixture was warmed to room temperature, cooled to -78° C. over a period of 2 hours, and treated with a neat solution of methyl iodide (5.68 g, 40 mmol).
The reaction mixture was warmed to room temperature overnight, then quenched with saturated NH4Cl (100 mL) at room temperature and extracted with ethyl acetate (100 mL).
The organic phase was washed with brine (100 mL), dried (MgSO4), filtered, and concentrated in vacuo to provide a yellow oil which was crystallized from hexane to provide the desired product as a slightly yellow solid (3.1 g, 81percent): 1H NMR (CDCl3) δ 0.79 (m, 2H), 1.36 (s, 9H), 1.52 (m, 2H), 1.62 (s, 3H), 4.10 (br s, 1H).
Reference: [1] Patent: US2006/183694, 2006, A1, . Location in patent: Page/Page column 25-26
[2] Patent: US2007/10455, 2007, A1, . Location in patent: Page/Page column 28
[3] Patent: US2008/14173, 2008, A1, . Location in patent: Page/Page column 27
  • 4
  • [ 74-88-4 ]
  • [ 669008-25-7 ]
Reference: [1] ChemMedChem, 2015, vol. 10, # 4, p. 727 - 735
[2] Patent: WO2012/40040, 2012, A1, . Location in patent: Page/Page column 35-36
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