Citric Acid → 3-[4-(azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)benzoic acid

HRID 20522노트

반응식

HRID 20522 반응식
[N:1]1([C:5]([C:7]2[CH:27]=[CH:26][C:10]([O:11][C:12]3[CH:13]=[C:14]([CH:18]=[C:19]([O:21][C@@H:22]([CH3:25])[CH2:23][OH:24])[CH:20]=3)[C:15]([OH:17])=[O:16])=[C:9]([F:28])[CH:8]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1.[Si:29](Cl)([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30].N1C=CN=C1.C(=O)(O)[O-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C.C(OCC)C.O>[N:1]1([C:5]([C:7]2[CH:27]=[CH:26][C:10]([O:11][C:12]3[CH:13]=[C:14]([CH:18]=[C:19]([O:21][C@@H:22]([CH3:25])[CH2:23][O:24][Si:29]([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30])[CH:20]=3)[C:15]([OH:17])=[O:16])=[C:9]([F:28])[CH:8]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1

참가 물질

9

반응물 5

HCID 311Citric AcidHCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 516892Sodium BicarbonateHCID 593468833-[4-(azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]benzoic acid

생성물 1

HCID 593469093-[4-(azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)benzoic acid

시약·촉매·용매 3

HCID 962Water용매HCID 3283Diethyl Ether용매HCID 6228Dimethylformamide용매

실험 절차

A mixture of 3-[4-(azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]benzoic acid (9.8 g, 0.025 mol), t-butyldimethylsilylchloride (11.3 g, 0.075 mol) and imidazole (17.08 g, 0.25 mol) in DMF (100 mL) was stirred at RT for 24 hours. Water (100 mL) was added and the mixture extracted into diethyl ether (3×100 mL). The extracts were combined and washed with water (3×100 mL), brine (100 mL), dried (MgSO4), filtered, and evaporated in vacuo to give a golden oil. Saturated aqueous sodium bicarbonate (100 mL) and diethyl ether (100 mL) were added and stirred for 30 mins. The aqueous layer was acidified with 1M citric acid solution and extracted into diethyl ether (3×100 mL). The extracts were combined, dried (MgSO4), filtered, and evaporated in vacuo and the crude product chromatographed on silica, eluting with ethyl acetate, to give the desired compound. (6.32 g).

후처리

  1. extractionthe mixture extracted into diethyl ether (3×100 mL)
  2. washwashed with water (3×100 mL), brine (100 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customto give a golden oil
  7. stirringstirred for 30 mins
  8. extractionextracted into diethyl ether (3×100 mL)
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. customevaporated in vacuo
  12. customthe crude product chromatographed on silica
  13. washeluting with ethyl acetate

출처 및 근거

ORD 기록
ord-159f422bd884422f8a95d077a5d152fa
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07745475B2

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