Potassium Carbonate → (5-Chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-phenylsulfamoyl)-acetic Acid

HRID 11634

반응식

HRID 11634 반응식
[NH2:1][C:2]1[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:3]=1[O:4][CH2:5][C:6]([N:8]1[CH2:13][C@H:12]([CH3:14])[N:11]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[CH2:10][C@H:9]1[CH3:23])=[O:7].C(=O)([O-])[O-].[K+].[K+].C([O:37][C:38](=[O:44])[CH2:39][S:40](Cl)(=[O:42])=[O:41])C.CN(C1C=CC=CN=1)C.O.[OH-].[Li+]>CN(C)C=O.C(OCC)(=O)C.O>[Cl:28][C:26]1[CH:25]=[CH:24][C:3]([O:4][CH2:5][C:6]([N:8]2[CH2:13][C@H:12]([CH3:14])[N:11]([CH2:15][C:16]3[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=3)[CH2:10][C@H:9]2[CH3:23])=[O:7])=[C:2]([NH:1][S:40]([CH2:39][C:38]([OH:44])=[O:37])(=[O:42])=[O:41])[CH:27]=1

참가 물질

9

반응물 5

HCID 11430Potassium CarbonateHCID 218852-DimethylaminopyridineHCID 168937Lithium hydroxide, monohydrateHCID 12225100Ethyl (chlorosulfonyl)acetateHCID 540805932-(2-amino-4-chloro-phenoxy)-1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-ethanone

생성물 1

HCID 69655531(5-Chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-phenylsulfamoyl)-acetic Acid

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매2회HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 2-(2-amino-4-chloro-phenoxy)-1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-ethanone (0.030 g, 0.074 mmol) in dimethylformamide (0.5 ml) was added potassium carbonate (0.030 g, 0.239 mmol), chlorosulfonyl-acetic acid ethyl ester (0.02 g, 0.12 mmol) (for preparation, see: Helv. Chim. Acta., (1997) 80, 671 and Bull. Soc. Chim. Fr. (1975), 807) in dimethylformamide (0.5 ml) and finally catalytic dimethylaminopyridine. After 23 hours the reaction was diluted with ethyl acetate and washed with pH 7.0 phosphate buffer (0.05 M). The organic layer was dried over magnesium sulfate, filtered and concentrated. The crude ester was then dissolved in 1:1 tetrahydrofuran:water (0.5 ml) and lithium hydroxide hydrate (0.004 g, 0.095 mmol) was added. After 19 hours the reaction was concentrated and the title compound purified by silica gel chromatography (0.006 g, LRMS: 528.3).

후처리

  1. washwashed with pH 7.0 phosphate buffer (0.05 M)
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe crude ester was then dissolved in 1:1 tetrahydrofuran
  6. concentrationAfter 19 hours the reaction was concentrated
  7. customthe title compound purified by silica gel chromatography (0.006 g, LRMS: 528.3)

출처 및 근거

ORD 기록
ord-51ce9bb9875247e18ea225cd6ad21a82
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07098212B2

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