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

HRID 59755ノート

反応式

HRID 59755 の反応式
[NH2:1][C:2]1[S:6][C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:4][C:3]=1[O:12][CH3:13].[CH3:14][S:15](Cl)(=[O:17])=[O:16].C([O-])([O-])=O.[K+].[K+].Cl.Cl[CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1>N1C=CC=CC=1>[CH3:13][O:12][C:3]1[CH:4]=[C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[S:6][C:2]=1[N:1]([CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)[S:15]([CH3:14])(=[O:17])=[O:16]

参加物

6

反応物 4

HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 77210Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1)HCID 86703860Ethyl 5-amino-4-methoxythiophene-2-carboxylate

生成物 1

HCID 86703862ethyl 4-methoxy-5-(N-(2-morpholinoethyl)-methylsulfonamido)thiophene-2-carboxylate

試薬・触媒・溶媒 1

HCID 1049Pyridine溶媒

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.

後処理

  1. customThe solvent was removed under vacuum
  2. washthe organic phase was washed with brine
  3. dry with materialdried over sodium sulfate
  4. customThe solvent was removed under vacuum
  5. dissolutionthe residue was dissolved in dry DMF (10 ml)
  6. temperaturethe resulting mixture was heated to 80° C.
  7. stirringstirred at this temperature for 3 hours
  8. customThe solvent was removed under vacuum
  9. dissolutionthe residue was dissolved in EtOAc
  10. washwashed with brine
  11. dry with materialThe organic phase was dried over sodium sulfate
  12. filtrationfiltered
  13. customevaporated
  14. filtrationThe residue was purified by filtration on silica gel cartridge (DCM/EtOAc=8/2 to EtOAc)

出典と根拠

ORDレコード
ord-6e651cd8e9914442964d96a4f08bcd4a
出典データセット
uspto-grants-2016_09
特許番号
US09440954B2

反応ノート

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