反応 #88033

反応方程式

K2CO3

4-(2-chloroethyl)morpholine hydrochloride

ethyl 5-amino-4-methoxythiophene-2-carboxylate

methanesulfonyl chloride

→

ethyl 4-methoxy-5-(N-(2-morpholinoethyl)-methylsulfonamido)thiophene-2-carboxylate

溶媒

pyridine

反応条件

後処理

1. 1
   その他The solvent was removed under vacuum
2. 2
   洗浄the organic phase was washed with brine
3. 3
   乾燥dried over sodium sulfate
4. 4
   その他The solvent was removed under vacuum
5. 5
   workup.DISSOLUTIONthe residue was dissolved in dry DMF (10 ml)
6. 6
   温度the resulting mixture was heated to 80° C.
7. 7
   workup.STIRRINGstirred at this temperature for 3 hours
8. 8
   その他The solvent was removed under vacuum
9. 9
   workup.DISSOLUTIONthe residue was dissolved in EtOAc
10. 10
    洗浄washed with brine
11. 11
    乾燥The organic phase was dried over sodium sulfate
12. 12
    ろ過filtered
13. 13
    その他evaporated
14. 14
    ろ過The residue was purified by filtration on silica gel cartridge (DCM/EtOAc=8/2 to EtOAc)

実験手順

To a solution of ethyl 5-amino-4-methoxythiophene-2-carboxylate (Int. 69) (261 mg, 1.297 mmol) (prepared as described in Step 5 hereabove reported) in pyridine (10 ml) cooled to 0° C., methanesulfonyl chloride (0.131 ml, 1.686 mmol) was added, and the reaction was allowed to warm to RT and stirred overnight. The solvent was removed under vacuum and the residue was portioned between EtOAc and 10% HCl; the organic phase was washed with brine and dried over sodium sulfate. The solvent was removed under vacuum and the residue was dissolved in dry DMF (10 ml); K2CO3 (448 mg, 3.24 mmol) and 4-(2-chloroethyl)morpholine hydrochloride (362 mg, 1.946 mmol) were added in one portion, and the resulting mixture was heated to 80° C. and stirred at this temperature for 3 hours. The solvent was removed under vacuum, and the residue was dissolved in EtOAc and washed with brine. The organic phase was dried over sodium sulfate, filtered evaporated. The residue was purified by filtration on silica gel cartridge (DCM/EtOAc=8/2 to EtOAc) to afford ethyl 4-methoxy-5-(N-(2-morpholinoethyl)-methylsulfonamido)thiophene-2-carboxylate (Int. 70) in a mixture with approximately 30% of corresponding methyl ester (375 mg, 0.955 mmol, MS/ESI+392.8 [MH]+). This intermediate was used as such in the following step considering it was a single product.

出典