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

HRID 20522ノート

反応式

HRID 20522 の反応式
[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

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 3283Diethyl Ether溶媒HCID 6228Dimethylformamide溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-159f422bd884422f8a95d077a5d152fa
出典データセット
uspto-grants-2010_06
特許番号
US07745475B2

反応ノート

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