Water → (1aRS,7bSR)-5-(2-{[((S)-1-ethylpyrrolidine-3-carbonyl)amino]methyl}-4-fluorobenzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid

HRID 927885노트

반응식

HRID 927885 반응식
[CH2:1]([N:3]1[CH2:7][CH2:6][C@H:5]([C:8]([NH:10][CH2:11][C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=2[S:19]([NH:22][C:23]2[C:32]([C:33]([O:35]C)=[O:34])=[C:31]3[C:26]([CH:27]4[CH2:37][CH:28]4[CH2:29][O:30]3)=[CH:25][CH:24]=2)(=[O:21])=[O:20])=[O:9])[CH2:4]1)[CH3:2].O.[OH-].[Li+].O>O1CCOCC1>[CH2:1]([N:3]1[CH2:7][CH2:6][C@H:5]([C:8]([NH:10][CH2:11][C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=2[S:19]([NH:22][C:23]2[C:32]([C:33]([OH:35])=[O:34])=[C:31]3[C:26]([CH:27]4[CH2:37][CH:28]4[CH2:29][O:30]3)=[CH:25][CH:24]=2)(=[O:20])=[O:21])=[O:9])[CH2:4]1)[CH3:2]

참가 물질

5

반응물 3

HCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 71006923Methyl (1aRS,7bSR)-5-(2-{[((S)-1-ethylpyrrolidine-3-carbonyl)amino]methyl}-4-fluoro-benzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate2회

생성물 1

HCID 86713266(1aRS,7bSR)-5-(2-{[((S)-1-ethylpyrrolidine-3-carbonyl)amino]methyl}-4-fluorobenzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid수율 49.7%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

Methyl (1aRS,7bSR)-5-(2-{[((S)-1-ethylpyrrolidine-3-carbonyl)amino]methyl}-4-fluoro-benzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 188, 0.190 g) and lithium hydroxide monohydrate (0.150 g) were suspended in dioxane (5 mL) and water (5 mL) and the mixture was stirred and heated at 100° C. for 18.5 hours. After cooling, the volatiles were removed in vacuo and the residue was acidified by addition of aqueous citric acid solution (10%) and extracted with DCM. 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 acetonitrile and water, containing 0.1% formic acid, with a gradient of 25-60% to give (1aRS,7bSR)-5-(2-{[((S)-1-ethylpyrrolidine-3-carbonyl)amino]methyl}-4-fluorobenzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid (0.092 g) as a white solid.

후처리

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

출처 및 근거

ORD 기록
ord-1114385454b94cb3a86f3fbe539785dc
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09290472B2

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