Water → (1aRS,7bSR)-5-[2-(1-ethylpiperidin-4-ylmethyl)-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid

HRID 927881ノート

反応式

HRID 927881 の反応式
[CH2:1]([N:3]1[CH2:8][CH2:7][CH:6]([CH2:9][C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=2[S:17]([NH:20][C:21]2[C:30]([C:31]([O:33]C)=[O:32])=[C:29]3[C:24]([CH:25]4[CH2:35][CH:26]4[CH2:27][O:28]3)=[CH:23][CH:22]=2)(=[O:19])=[O:18])[CH2:5][CH2:4]1)[CH3:2].O.[OH-].[Li+].O>O1CCOCC1>[CH2:1]([N:3]1[CH2:8][CH2:7][CH:6]([CH2:9][C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=2[S:17]([NH:20][C:21]2[C:30]([C:31]([OH:33])=[O:32])=[C:29]3[C:24]([CH:25]4[CH2:35][CH:26]4[CH2:27][O:28]3)=[CH:23][CH:22]=2)(=[O:18])=[O:19])[CH2:5][CH2:4]1)[CH3:2]

参加物

5

反応物 3

HCID 962WaterHCID 168937Lithium hydroxide, monohydrate2 回HCID 86713265Methyl (1aRS,7bSR)-5-[2-(1-ethylpiperidin-4-ylmethyl)-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate2 回

生成物 1

HCID 78078739(1aRS,7bSR)-5-[2-(1-ethylpiperidin-4-ylmethyl)-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid収率 43.1%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

Methyl (1aRS,7bSR)-5-[2-(1-ethylpiperidin-4-ylmethyl)-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 177, 0.279 g) and lithium hydroxide monohydrate (0.233 g) were suspended in dioxane (7 mL) and water (3 mL) and the mixture was stirred and heated at 80° C. for 25 hours. Further lithium hydroxide monohydrate (0.116 g) was added and the mixture heating was continued for 18 hours. After cooling, the volatiles were removed in vacuo, the residue was acidified by addition of aqueous citric acid solution (10%) and saturated with sodium chloride. The mixture was extracted with DCM and the organic layer was dried (Na2SO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by preparative HPLC (C18), eluting with a mixture of methanol and water, containing 0.1% formic acid, with a gradient of 10-98% to give (1aRS,7bSR)-5-[2-(1-ethylpiperidin-4-ylmethyl)-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid (0.117 g) as a white solid.

後処理

  1. temperaturethe mixture heating
  2. temperatureAfter cooling
  3. customthe volatiles were removed in vacuo
  4. additionthe residue was acidified by addition of aqueous citric acid solution (10%) and saturated with sodium chloride
  5. extractionThe mixture was extracted with DCM
  6. dry with materialthe organic layer was dried (Na2SO4)
  7. filtrationfiltered
  8. customThe filtrate was evaporated to dryness
  9. customthe residue was purified by preparative HPLC (C18)
  10. washeluting with a mixture of methanol and water
  11. additioncontaining 0.1% formic acid

出典と根拠

ORDレコード
ord-b96281aef31642449c072f8d2079e8af
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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