Hydrochloric Acid → {[4-(4-Fluoro-phenoxy)-benzenesulphonyl]-hydroxycarbamoylmethyl-amino}-acetic acid

HRID 37747ノート

反応式

HRID 37747 の反応式
C([O:5][C:6](=O)[CH2:7][N:8]([S:17]([C:20]1[CH:25]=[CH:24][C:23]([O:26][C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)=[CH:22][CH:21]=1)(=[O:19])=[O:18])[CH2:9][C:10]([O:12]C(C)(C)C)=[O:11])(C)(C)C.CN1CCOCC1.[NH2:42][OH:43].Cl.[OH-].[K+]>C1COCC1.CO>[F:33][C:30]1[CH:31]=[CH:32][C:27]([O:26][C:23]2[CH:24]=[CH:25][C:20]([S:17]([N:8]([CH2:9][C:10]([OH:12])=[O:11])[CH2:7][C:6](=[O:5])[NH:42][OH:43])(=[O:19])=[O:18])=[CH:21][CH:22]=2)=[CH:28][CH:29]=1

参加物

8

反応物 5

HCID 313Hydrochloric AcidHCID 787HydroxylamineHCID 79724-MethylmorpholineHCID 14797Potassium HydroxideHCID 67312951{[4-(4-Fluoro-phenoxy)-benzenesulphonyl]-tert-butoxycarbonylmethyl-amino}-aceticacid tert-butyl ester

生成物 1

HCID 86655169{[4-(4-Fluoro-phenoxy)-benzenesulphonyl]-hydroxycarbamoylmethyl-amino}-acetic acid

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

{Carboxymethyl-[4-(4-bromo-phenoxy)-benzenesulphonyl]-amino}-acetic acid (4b) (500 mg, 1.30 mmol) was dissolved in dry THF (10 mL). ECF (100 μL, 1.12 mmol), and NMM (120 μL, 1.12 mmol) were added and stirred for 40 min at 0° C. NH2OH×HCl (90 mg, 1.30 mmol) and KOH (73 mg, 1.30 mmol) were dissolved in dry MeOH (10 mL) and stirred at 0° C. for 30 min. The solids were filtered off, and the THF solution was added dropwise to the methanol filtrate and stirred for 2 h at 0° C. The reaction mixture was filtered, the solvent evaporated, and the residue dissolved in H2O (25 mL). After adjusting the pH to 1-2, the aqueous layer was extracted with EtOAc (3×30 mL). The combined organic layers were dried over MgSO4, evaporated in vacuo, and co-evaporated with EtOAc (3×3 mL) to yield the pure product as light-pink solid. Yield: 267 mg, 0.67 mmol, 52%. 1H-NMR (DMSO-d6): δ 7.91 (dd, 2H, 3JHH=9.0 Hz, 4JHF=5.1 Hz, ArH), 7.42 (t, 2H, 3JHH=9.0 Hz, 3JHF=9.0 Hz, ArH), 4.07 (s, 4H, 2×CH2CO2H). ESI-MS calcd for C16H15FN2O7S 398.06 [M-H]−, obsd 399.10

後処理

  1. stirringstirred at 0° C. for 30 min
  2. filtrationThe solids were filtered off
  3. additionthe THF solution was added dropwise to the methanol filtrate
  4. stirringstirred for 2 h at 0° C
  5. filtrationThe reaction mixture was filtered
  6. customthe solvent evaporated
  7. dissolutionthe residue dissolved in H2O (25 mL)
  8. extractionthe aqueous layer was extracted with EtOAc (3×30 mL)
  9. dry with materialThe combined organic layers were dried over MgSO4
  10. customevaporated in vacuo

出典と根拠

ORDレコード
ord-15cc2432937f4a4fa26680a4469c154a
出典データセット
uspto-grants-2013_09
特許番号
US08524194B2

反応ノート

読み込み中…