tert-Butanol → N-(t-butoxycarbonylsulfamoyl)-N-(2-benzyloxy-6-fluorophenyl)glycine methyl ester

HRID 889272ノート

反応式

HRID 889272 の反応式
Cl[S:2]([N:5]=[C:6]=[O:7])(=[O:4])=[O:3].[C:8]([OH:12])([CH3:11])([CH3:10])[CH3:9].[CH2:13]([O:20][C:21]1[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[C:22]=1[NH:23][CH2:24][C:25]([O:27][CH3:28])=[O:26])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.CCN(C(C)C)C(C)C>ClCCl>[CH3:28][O:27][C:25](=[O:26])[CH2:24][N:23]([S:2](=[O:4])(=[O:3])[NH:5][C:6]([O:12][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:7])[C:22]1[C:29]([F:33])=[CH:30][CH:31]=[CH:32][C:21]=1[O:20][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

参加物

6

反応物 4

HCID 6386tert-ButanolHCID 70918Chlorosulfonyl isocyanateHCID 81531DiisopropylethylamineHCID 68430918Methyl 2-(2-benzyloxy-6-fluoroanilino)-acetate

生成物 1

HCID 68429517N-(t-butoxycarbonylsulfamoyl)-N-(2-benzyloxy-6-fluorophenyl)glycine methyl ester

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒3 回

実験手順

Chlorosulfonylisocyanate (379 μL, 616 mg, 4.36 mmol) is dissolved in dichloromethane (5 mL) cooled in an ice bath. To this is added a solution of tert.-butanol (416 μL, 322 mg, 4.35 mmol) in dichloromethane (2 mL) dropwise then the mixture is stirred cold for 5 min then 15 min at RT. To the rechilled solution is added dropwise a solution of methyl 2-(2-benzyloxy-6-fluoroanilino)-acetate (840 mg, 2.90 mmol) and Hunig's base (859 μL, 637 mg, 4.93 mmol) in dichloromethane and the resulting solution allowed to warm to RT. After 4 h LC/MS showed the reaction to be complete. The solution is extracted with water, and the organic layer dried, filtered, and solvent removed under reduced pressure. The residual material is chromatographed on an Isco Companion (80 g silica gel, 20-50% gradient of hexane/ethyl acetate) to afford N-(t-butoxycarbonylsulfamoyl)-N-(2-benzyloxy-6-fluorophenyl)glycine methyl ester as an oil. MS (M−1)−=467; NMR (CDCl3): δ 7.51 (br s, 1H), 7.40 (m, 5H), 7.24 (m, 2H), 6.78 (m, 2H), 5.16 (s, 2H), 4.60 (dd, J=101 and 18 Hz, 2H), 3.64 (s, 3H), 1.46 (s, 9H).

後処理

  1. temperaturecooled in an ice bath
  2. custom15 min
  3. customat RT
  4. waitAfter 4 h LC/MS showed
  5. customthe reaction
  6. extractionThe solution is extracted with water
  7. customthe organic layer dried
  8. filtrationfiltered
  9. customsolvent removed under reduced pressure
  10. customThe residual material is chromatographed on an Isco Companion (80 g silica gel, 20-50% gradient of hexane/ethyl acetate)

出典と根拠

ORDレコード
ord-d50bcf1b15da4f25802579f84fe87f7c
出典データセット
uspto-grants-2012_08
特許番号
US08252820B2

反応ノート

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