Sodium Hydroxide → (R)-di-tert-butyl 2-(ethyl(4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butyl)amino)ethyl phosphate

HRID 1476288노트

반응식

HRID 1476288 반응식
[P:1]([O:13][CH2:14][CH2:15][NH:16][CH2:17][CH3:18])([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].O=[CH:20][CH2:21][C@@H:22]([NH:31][C:32]1[CH:37]=[CH:36][C:35]([S:38]([NH2:41])(=[O:40])=[O:39])=[CH:34][C:33]=1[S:42]([C:45]([F:48])([F:47])[F:46])(=[O:44])=[O:43])[CH2:23][S:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCCl.C(Cl)Cl>[P:1]([O:13][CH2:14][CH2:15][N:16]([CH2:17][CH3:18])[CH2:20][CH2:21][C@@H:22]([NH:31][C:32]1[CH:37]=[CH:36][C:35]([S:38](=[O:39])(=[O:40])[NH2:41])=[CH:34][C:33]=1[S:42]([C:45]([F:48])([F:46])[F:47])(=[O:43])=[O:44])[CH2:23][S:24][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])([O:8][C:9]([CH3:10])([CH3:11])[CH3:12])=[O:2]

참가 물질

7

반응물 4

HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 58080210Di-tert-butyl 2-(ethylamino)ethyl phosphate2회HCID 86661872(R)-4-(4-oxo-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide2회

생성물 1

HCID 66723800(R)-di-tert-butyl 2-(ethyl(4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butyl)amino)ethyl phosphate수율 50.4%

시약·촉매·용매 2

HCID 111,2-Dichloroethane용매2회HCID 6344Dichloromethane용매

실험 절차

A solution of di-tert-butyl 2-(ethylamino)ethyl phosphate (INTERMEDIATE 49, 455 mg, 1.62 mmol) in 1,2-dichloroethane (0.5 ml) at r.t was added to a solution (R)-4-(4-oxo-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide (INTERMEDIATE 45, 0.78 g, 1.62 mmol) and 1,2-dichloroethane (10.0 ml). The resulting reaction mixture was stirred for 15 minutes at r.t and solid sodium triacetoxyborohydride (0.514 g, 2.42 mmol) was added. The resulting mixture was stirred at r.t for 4 hours. A solution of NaOH (aq., 0.5 N, 40 ml) and DCM (20 ml) were added to the reaction mixture. After stirring for 15 min at r.t, the layers were separated. After separation, the organic layer was washed with saturated NaHCO3, brine, dried (Na2SO4), and concentrated in vacuo. The concentrate was purified by column chromatography (ISCO, silica gel, eluting with 0→100% EtOAc/hexanes) to give the title compound (610 mg, yield: 50%).

후처리

  1. customThe resulting reaction mixture
  2. additionwas added
  3. stirringAfter stirring for 15 min at r.t
  4. customthe layers were separated
  5. customAfter separation
  6. washthe organic layer was washed with saturated NaHCO3, brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customThe concentrate was purified by column chromatography (ISCO, silica gel, eluting with 0→100% EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-b7a6865c071b4ec5a30407c5866cc2c0
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09018381B2

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