5-Chlorothiophene-3-carbo...

To a solution of thiophene-3-carbaldehyde (20.0 g, 178.3 mmol) and N-chlorosuccinimide (23.8 g, 178.3 mmol) in AcOH (180 mL) was stirred at 110 °C for 4 hours. After the completion of reaction, the solution was cooled to room temperature, and then was diluted with EtOAc (120 mL), washed with H£6L ?(RI '5) tE6 2 (9p-oswu 'ZRN oot) WIN RT (percento6' FE) PJaA MOJJa( ajUd U SU (01) auajj AU QuatpU1SauUxaJ'oyQ3 percentoc-percentoE) £qdU1OwwO1qo JSU £q uot-Uogun alnSSald paonpai iapun pawauaouoo UU tOStUNSflO1p(quU laAo paup SUM IaJ(UJ otUU1Q Qw os) arnaop(a UU (jw os) OtR uaaaq pauotpnUd puU alnSSaldpaonpai iapun papmuaouoo tN iapun Srnoq o IOJ D00L U 1fl3S SUM ainjxnu uOl3oUal aj Qowm 9L0 ' oo) Eq SUM (jounu OE 'R01d1 U' w) EQy 'Qoanu810 ' too) t(°vo)Pd 'Qoww 91 ' oE) (6) ap(qapJUutJ-OotdOwOlq-9 'Qoanu 091 ' tLi (5) ptcrn otuOlOqQi(utAp(-xajopi(o-j-() jo ainpctw PW1flJUS UO1U UU oi :1 dais(Rd 'm) 0IU9EI ?(Rd 'w) SdI-tSI ?(RI 'w) 9I9 ?(RI 'ZR 91=1 'P) td9 ?(RI 'ZR 091 '89=f 'PP) 98L ?(RI 'ZR T8=1 'P) 69L ?(RI 'ZR T8=1 'P) ILL ?(RI 'ZR 9L=f '1) Step 1: Coupling of (E)-(2-cyclohexylvinyl)boronic acid with REFERENTIAL EXAMPLE 343 Ethyl 2-azido-3-(5-chlorothien-3-yl)acrylate: After ethanol (15 ml) was added to a 20percent ethanol solution (10.7 ml) of sodium ethoxide, and the mixture was cooled to 0° C., a mixture of the compound (1.01 g) obtained in Referential Example 342 and ethyl azidoacetate (3.55 g) was added dropwise over 30 minutes, and the resultant mixture was stirred at 0° C. for 3 hours. A cooled aqueous solution of ammonium chloride was added to the reaction mixture to conduct extraction 3 times with diethyl ether. Organic layers were combined, and the solvent was distilled off under reduced pressure. The residue was purified by flach column chromatagraphy on silica gel (ethyl acetate:hexane=1:49) to obtain the title compound (1.04 g). 1H-NMR (CDCl3) delta: 1.38(3H, t, J=7.1 Hz), 4.34(2H, q, J=7.1 Hz), 6.75(1H, s), 7.39(1H, d, J=1.7 Hz), 7.54(1H, d, J=1.7 Hz).After ethanol (15 mL) was added to a 20percent ethanol solution (10.7 mL) of sodium ethoxide, and the mixture was cooled to 0°C, a mixture of the compound (1.01 g) obtained in Referential Example 342 and ethyl azidoacetate (3.55 g) was added dropwise over 30 minutes, and the resultant mixture was stirred at 0°C for 3 hours. A cooled aqueous ammonium chloride was added to the reaction mixture, and the resultant mixture was extracted 3 times with diethyl ether. The organic layers were combined, and the solvent was distilled away under reduced pressure. The residue was purified by flash silica gel column chromatography (ethyl acetate : hexane = 1:49), to thereby give the title compound (1.04 g).1H-NMR(CDCl3) delta:1.38(3H, t, J=7.1Hz), 4.34(2H, q, J=7.1Hz), 6.75(1H, s), 7.39(1H, d, J=1.7Hz), 7.54(1H, d, J=1.7Hz).The compound (5.17 g) obtained in Referential Example 341 was dissolved in methylene chloride (400 mL), and manganese dioxide (51.3 g) was added to the solution, followed by stirring at room temperature for 15 hours. After the reaction mixture was filtered, the solvent was distilled away under reduced pressure, to thereby give the title compound (2.84 g).1H-NMR(CDCl3) delta:7.35(1H, d, J=1.7Hz), 7.88(1H, d, J=1.7Hz), 9.75(1H, s).REFERENTIAL EXAMPLE 342 5-Chlorothiophene-3-carbaldehyde: The compound (5.17 g) obtained in Referential Example 341 was dissolved in methylene chloride (400 ml), and manganese dioxide (51.3 g) was added to stir the mixture at room temperature for 15 hours. After the reaction mixture was filtered, the solvent was distilled off under reduced pressure to obtain the title compound (2.84 g). 1H-NMR (CDCl3) delta: 7.35(1H, d, J=1.7 Hz), 7.88(1H, d, J=1.7 Hz), 9.75(1H, s).[Referential Example 342] 5-Chlorothiophene-3-carbaldehyde: The compound (5.17 g) obtained in Referential Example 341 was dissolved in methylene chloride (400 ml), and manganese dioxide (51.3 g) was added to stir the mixture at room temperature for 15 hours.. After the reaction mixture was filtered, the solvent was distilled off under reduced pressure to obtain the title compound (2.84 g).1H-NMR (CDCl3) delta: 7.35(1H, d, J=1.7Hz), 7.88(1H, d, J=1.7Hz), 9.75(1H, s).[Referential Example 343] ethyl 2-azido-3-(5-chlorothien-3-yl)acrylate: After ethanol (15 ml) was added to a 20percent ethanol solution (10.7 ml) of sodium ethoxide, and the mixture was cooled to 0°C, a mixture of the compound (1.01 g) obtained in Referential Example 342 and ethyl azidoacetate (3.55 g) was added dropwise over 30 minutes, and the resultant mixture was stirred at 0°C for 3 hours.. A cooled aqueous solution of ammonium chloride was added to the reaction mixture to conduct extraction 3 times with diethyl ether.. Organic layers were combined, and the solvent was distilled off under reduced pressure.. The residue was purified by flach column chromatagraphy on silica gel (ethyl acetate:hexane = 1:49) to obtain the title compound (1.04 g).1H-NMR (CDCl3) delta: 1.38(3H, t, J=7.1Hz), 4.34(2H, q, J=7.1Hz), 6.75(1H, s), 7.39(1H, d, J=1.7Hz), 7.54(1H, d, J=1.7Hz).

Molecular Weight:146.60
XLogP3:2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:145.9593136
Monoisotopic Mass:145.9593136
Topological Polar Surface Area:45.3
Heavy Atom Count:8
Complexity:96.4
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes