Butyl Cyclopropanesulfonate

Colourless Oil

Step A: 1-Butyl cvclopropanesulfonateCyclopropanesulfonyl chloride (25g, 178 mmol, leq) was dissolved in an excess of n-BuOH (80ml) and the reaction mixture was cooled at OCyclopropyl sulfonyl chloride (2 g, 14.2 mmol) was added drop-wise at 0° C. to a solution of Butylalcohol (2.1 g, 28.4 mmol) and Pyridine (2.35 g, 29.8 mmol) in DCM (20 mL) and continued stifling at 25° C. for 16 h. The reaction mixture was diluted with DCM (100 mL), washed with 1N aq.HCl solution followed by water and brine Organic layer collected was dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford the Benzyl cyclopropanesulfonate (1.8 g, 72percent yield). Step A: Butyl cyclopropanesulfonate:Cyclopropanesulfonyl chloride (5 g, 35 mmole, 1 eq) was dissolved in an excess BuOH (20 ml), the reaction mixture was cooled at -10 Cyclopropanesulfonyl chloride (5 g, 35 mmol, 1 eq) was dissolved in an excess BuO l (20 ml), the reaction mixture was cooled at -10°C and pyridine (5.8 mL, 70 mmol, 2 eq) was slowly added dropwise. The mixture was slowly warmed at room temperature and stirred overnight. The solvent was removed under reduced pressure and the resulting white solid was dissolved in CHCI3. The organic phase was washed with water, brine and dried (MgS04) and concentrated to give an oil (4.8 g, 24.9 mmol, 71percent). i i NMR (300 MHz, CDCI3): δ 4.25 (t, 2H), 2.46 (m, 1H), 1.74 (m, 2H), 1.45 (m, 2H), 1.25 (dd, 2H), 1.09 (dd, 2H), .93 (t, 3H).n-BuLi (0.78 g, 12.25 mmol) was added drop-wise at '78° C. to a solution of Butylcyclopropane sulfonate (2.0 g, 11.2 mmol) in THF (20 mL) and continued stirring at the same temperature for 10 min. CH3I (3.98 g, 28.0 mmol) was added at '78° C., allowed the reaction to warm to 0° C. with stirring for 30 min. The reaction mixture was quenched with ice cold water, diluted with ethylacetate (100 mL), organic layer collected was dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford the crude. The crude was purified by column chromatography (using silica gel and 4percent ethyl acetate in Hexane as eluent) to afford benzyl 1-methylcyclopropane-1-sulfonate (Int-48) (2.0 g, 93percent yield). 1H NMR (300 MHz, CD3OD) delta 4.2-4.1 (2H, t), 1.7-1.6 (2H, m), 1.4 (3H, s), 1.5-1.3 (2H, m), 1.3-1.2 (2H, m), 1.0-0.9 (2H, m), 0.9 (3H, t) ppm.: General Procedure for the synthesis of substituted Butyl 1 -[2- hydroxypropyljcyclopropanesulfonates (GP1 ) :A solution of butyl cyclopropanesulfonate 2 (1 .2 g, 6.7 mmol) in THF (24 mL) was cooled to -78 C and n-butyllithium (1 .6M in n-hexane, 5.0 mL, 8.1 mmol) was added within 5 min. The mixture was stirred for 30 min and epoxypropane derivative 1 or 8 (8.1 mmol) was added followed by addition of boron tri fluoride diethyl etherate (0.84 mL, 6.7 mmol). The solution was stirred for 1 h at -78 C, the cooling bath was removed and stirring was continued for 2 additional hours. For aqueous work-up diluted hydrochloric acid (10percent, 0.8 mL), water (10 mL) and ethyl acetate (20 mL) were added. The organic layer was concentrated at 40 C to afford the corresponding butyl 1 -[2- hydroxypropyl]cyclopropanesulfonate 3.According to GP1 the following compounds were prepared : a : Butyl 1 -[(2S)-3-chloro-2-hydroxypropyl]cyclopropanesulfonate(S)-3(S)-3 was obtained from (S)-epichlorohydrin (S)-1 in 81 .3percent yield.Rf: 0.19 (silica gel, n-hexane/ethyl acetate 3: 1 )MS (DCI): m/z = 288.0 [M+NH4]+(100), 271 [M+H]+(14)1H NMR (400 MHz, Chloroform-d) delta = 0.90 - 1 .04 (m, 4 H) 1 .1 5 - 1 .23 (m, 1 H) 1 .39 - 1 .57 (m, 4 H) 1 .67 - 1 .80 (m, 2 H) 1 .90 (dd, J=15.28, 8.68 Hz, 1 H) 2.15 (dd, J=15.41 , 3.67 Hz, 1 H) 2.5 - 3.0 (br. s, 2H) 3.51 - 3.73 (m, 2 H) 4.13 - 4.34 (m, 3 H) ppmStep B: 1 -Step B:Butyl. 1-allylcyclopropane-1-sulfonateTo a solution of Step A:Step B: Butyl 1 -allylcyclopropane- 1 -sulfonate :To a solution of 1 -butyl cyclopropanesulfonate (4.8 g, 24.9 mmole) in THF at- 780C was added simultaneously butyllithium solution (15. 6 ml, 24.9 mmol, 1.6M, THF) and allyl iodide (24.9 mmole) under nitrogen atmosphere. The reaction mixture was stirred 2 hours at 780C and 3 hours at room tempoerature. The volatiles were evaporated under reduced EPO To a solution of 1 -butyl cyclopropanesulfonate (4.8 g, 24.9 mmol) in Ti ll- at -78°C was added simultaneously butyllithium solution (15.6 ml, 24.9 mmol, 1.6M, THF) and allyl iodide (24.9 mmol) under nitrogen atmosphere. The reaction mixture was stirred 2 hours at -78°C and 3 hours at room temperature. The volatiles were evaporated under reduced pressure and the residue extracted with CH2CI2 (100 ml). The extract was washed with water, dried (MgSQt) and evaporated. The residue was purified over silica gel chromatography (eluants: hexane/ CH2CI2) to obtain the titled product (3.75 g, 69.0percent) as a colorless oil. I NMR (300 MHz, CDCI3): delta 5.6 (m, 1H), 5.13-5.08 (t, 2H), 4.21 (t, 2H), 2.65 (d, 2H), 1.7 (m, 2H), 1.4 (m, 4H), .93 (m, 5H).191] Step B: Butyl 1-allylcvclopropane-l -sulfonateTo a solution of 1 -butyl cyclopropanesulfonate (6Og, 337mmol ) in THF (500ml) at -780C was slowly added butyllithium (150ml, 2.5M in hexane, 404mmol) under a nitrogen atmosphere. After stirring 15 minutes, allyl iodide (31ml, 337mmol) in THF (100ml) was added. The reaction mixture was stirred for 2 hours at -780C and 30 minutes at room temperature. The volatiles were evaporated under reduced pressure and the residue extracted with dichloromethane. The extract was washed with water, dried (MgSO4) and evaporated. The residue was purified via column chromatography on silica gel (eluent: PE/EA=10:l) to obtain the titled compound (5Og, yield:68percent) as a colorless oil. 1H NMR (400MHz, CDCl3) delta 5.71-5.81 (m, IH), 5.09-5.14 (m, 2H), 4.22(t, J= 6.4Hz, 2H), 2.65 (d, J= 7.2Hz, 2H), 1.74 (m, 2H), 1.42 (m, 4H), 0.91 (m, 5H);[190] Step A: 1-Butyl cvclopropanesulfonateCyclopropanesulfonyl chloride (25g, 178 mmol, leq) was dissolved in an excess of n-BuOH (80ml) and the reaction mixture was cooled at O0C, followed by the dropwise addition of pyridine (13.3ml, 160 mmol, 0.9eq). The mixture was slowly warmed to room temperature and stirred for 36 hours. The solvent was removed under reduced pressure and the resulting white solid was dissolved in chloroform. The organic phase was washed with water, brine and dried (MgSO4) and then concentrated to give an oil (24.5g, 77percent).1H NMR (400MHz, CDCl3) delta 4.25 (t, J= 6.4Hz, 2H), 2.47 (heptet, 2H), 1.74 (quintet, 2H), 1.43 (sextet, 2H), 1.24 (m, 2H), 1.08 (m, 2H), 0.96 (t, J = 7.6Hz, 3H);Cyclopropyl sulfonyl chloride (2 g, 14.2 mmol) was added drop-wise at 0° C. to a solution of Butylalcohol (2.1 g, 28.4 mmol) and Pyridine (2.35 g, 29.8 mmol) in DCM (20 mL) and continued stifling at 25° C. for 16 h. The reaction mixture was diluted with DCM (100 mL), washed with 1N aq.HCl solution followed by water and brine Organic layer collected was dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford the Benzyl cyclopropanesulfonate (1.8 g, 72percent yield). 1H NMR (300 MHz, CD3OD) delta 4.3-4.1 (2H, t), 2.7-2.6 (1H, m), 1.8-1.6 (2H, m), 1.6-1.4 (2H, m), 1.2-1.1 (4H, m), 1.0-0.9 (3H, t) ppm.Step A: Cyclopropanesulfonyl chloride (5 g, 35 mmol, 1 eq) was dissolved in an excess BuO l (20 ml), the reaction mixture was cooled at -10°C and pyridine (5.8 mL, 70 mmol, 2 eq) was slowly added dropwise. The mixture was slowly warmed at room temperature and stirred overnight. The solvent was removed under reduced pressure and the resulting white solid was dissolved in CHCI3. The organic phase was washed with water, brine and dried (MgS04) and concentrated to give an oil (4.8 g, 24.9 mmol, 71percent). i i NMR (300 MHz, CDCI3): delta 4.25 (t, 2H), 2.46 (m, 1H), 1.74 (m, 2H), 1.45 (m, 2H), 1.25 (dd, 2H), 1.09 (dd, 2H), .93 (t, 3H).

Molecular Weight:178.25
XLogP3:1.5
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:5
Exact Mass:178.06636548
Monoisotopic Mass:178.06636548
Topological Polar Surface Area:51.8
Heavy Atom Count:11
Complexity:198
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes