Triethylamine → methyl (1aRS,7bSR)-5-{N-[methoxycarbonyl]-N-[2-(4-chlorobutyryl-amino)-4-fluorobenzenesulfonyl]amino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate

HRID 927989ノート

反応式

HRID 927989 の反応式
[Cl:1][CH2:2][CH2:3][CH2:4][C:5](Cl)=[O:6].[CH3:8][O:9][C:10]([N:12]([C:24]1[C:33]([C:34]([O:36][CH3:37])=[O:35])=[C:32]2[C:27]([CH:28]3[CH2:38][CH:29]3[CH2:30][O:31]2)=[CH:26][CH:25]=1)[S:13]([C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=1[NH2:23])(=[O:15])=[O:14])=[O:11].C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>C1COCC1>[CH3:8][O:9][C:10]([N:12]([C:24]1[C:33]([C:34]([O:36][CH3:37])=[O:35])=[C:32]2[C:27]([CH:28]3[CH2:38][CH:29]3[CH2:30][O:31]2)=[CH:26][CH:25]=1)[S:13]([C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=1[NH:23][C:5](=[O:6])[CH2:4][CH2:3][CH2:2][Cl:1])(=[O:14])=[O:15])=[O:11]

参加物

6

反応物 4

HCID 8471TriethylamineHCID 783704-Chlorobutyryl chlorideHCID 516892Sodium BicarbonateHCID 86713323methyl (1aRS,7bSR)-5-[N-(methoxycarbonyl)-N-(2-amino-4-fluorobenzenesulfonyl)amino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate2 回

生成物 1

HCID 86713322methyl (1aRS,7bSR)-5-{N-[methoxycarbonyl]-N-[2-(4-chlorobutyryl-amino)-4-fluorobenzenesulfonyl]amino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate収率 90.2%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

4-Chlorobutyryl chloride (3.0 g) was added to a stirred, cooled solution of methyl (1aRS,7bSR)-5-[N-(methoxycarbonyl)-N-(2-amino-4-fluorobenzenesulfonyl]amino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate (Intermediate 110, 0.135 g) and triethylamine (1.0 g) in THF (10 mL) at 0° C. On completion of the addition, the mixture was stirred at room temperature for 4 hours. Saturated aqueous sodium bicarbonate was added and the mixture was extracted with ethyl acetate, dried (Na2SO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and petroleum ether, with a gradient of 20-25% to give methyl (1aRS,7bSR)-5-{N-[methoxycarbonyl]-N-[2-(4-chlorobutyrylamino)-4-fluoro-benzenesulfonyl]amino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate (0.15 g) as a yellow oil.

後処理

  1. additionOn completion of the addition
  2. extractionthe mixture was extracted with ethyl acetate
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customThe filtrate was evaporated to dryness
  6. customthe residue was purified by chromatography on silica
  7. washeluting with a mixture of ethyl acetate and petroleum ether, with a gradient of 20-25%

出典と根拠

ORDレコード
ord-a0b25da223354251ba1fe580f2772d14
出典データセット
uspto-grants-2016_03
特許番号
US09290472B2

反応ノート

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