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

Reaction equation

HRID 11634 reaction equation
[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

Participants

9

Reactant 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

Product 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

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-51ce9bb9875247e18ea225cd6ad21a82
Source dataset
uspto-grants-2006_08
Patent number
US07098212B2

Linked notes

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