Cesium carbonate → 3-[4-(azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]benzoic acid

HRID 20523

반응식

HRID 20523 반응식
[OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([O:12][C@@H:13]([CH3:16])[CH2:14][OH:15])[CH:11]=1)[C:5]([O:7]C)=[O:6].C(=O)([O-])[O-].[Cs+].[Cs+].[F:23][C:24]1[CH:25]=[C:26]([CH:33]=[CH:34][C:35]=1F)[C:27]([N:29]1[CH2:32][CH2:31][CH2:30]1)=[O:28].O.[OH-].[Li+]>CC(N(C)C)=O.O.C(OCC)C.C(OCC)(=O)C>[N:29]1([C:27]([C:26]2[CH:33]=[CH:34][C:35]([O:1][C:2]3[CH:3]=[C:4]([CH:9]=[C:10]([O:12][C@@H:13]([CH3:16])[CH2:14][OH:15])[CH:11]=3)[C:5]([OH:7])=[O:6])=[C:24]([F:23])[CH:25]=2)=[O:28])[CH2:32][CH2:31][CH2:30]1

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 168937Lithium hydroxide, monohydrateHCID 59127187methyl 3-hydroxy-5-[(1S)-2-hydroxy-1-methylethoxy]benzoateHCID 593468591-(3,4-Difluorobenzoyl)azetidine

생성물 1

HCID 593468833-[4-(azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]benzoic acid

시약·촉매·용매 3

HCID 962Water용매3회HCID 31374Dimethylacetamide용매HCID 21584169Diethylether ethylacetate용매

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온도
120 °C

실험 절차

A suspension of methyl 3-hydroxy-5-[(1S)-2-hydroxy-1-methylethoxy]benzoate (10.65 g, 0.047 mmol), cesium carbonate (30.71 g, 0.094 mol) and 1-(3,4-difluorobenzoyl)azetidine (9.28 g, 0.047 mol) in dimethylacetamide (80 mL) was heated at 120° C. for 22 hours. The reaction mixture was cooled and water (60 mL) added followed by lithium hydroxide monohydrate (1.97 g, 0.047 mol) in water (45 mL). The reaction was stirred for a further 24 hours. Water (100 mL) was added and the mixture extracted with ethyl acetate (3×50 mL) to remove any ester. The aqueous layer was acidified and extracted into ethyl acetate (5×50 mL). The extracts were combined and washed with water (100 mL), brine (100 mL), dried (MgSO4), filtered, and evaporated in vacuo to give a yellow liquid. A diethyl ether/ethyl acetate mixture (3:1) was added and the solution washed with water (100 mL), brine (100 mL), dried (MgSO4), filtered and evaporated in vacuo to give the desired compound. (9.8 g)

후처리

  1. temperatureThe reaction mixture was cooled
  2. extractionthe mixture extracted with ethyl acetate (3×50 mL)
  3. customto remove any ester
  4. extractionextracted into ethyl acetate (5×50 mL)
  5. washwashed with water (100 mL), brine (100 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customto give a yellow liquid
  10. washthe solution washed with water (100 mL), brine (100 mL)
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. customevaporated in vacuo

출처 및 근거

ORD 기록
ord-fb96a22953a74262a19670280383b308
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07745475B2

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