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

反応式

HRID 11634 の反応式
[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

参加物

9

反応物 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

生成物 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

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-51ce9bb9875247e18ea225cd6ad21a82
出典データセット
uspto-grants-2006_08
特許番号
US07098212B2

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