Sodium Hydroxide → (R)-di-tert-butyl 2-(4-(4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butyl)piperazin-1-yl)ethyl phosphate

HRID 1476296ノート

反応式

HRID 1476296 の反応式
[P:1]([O:13][CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1)([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].O=[CH:23][CH2:24][C@@H:25]([NH:34][C:35]1[CH:40]=[CH:39][C:38]([S:41]([NH2:44])(=[O:43])=[O:42])=[CH:37][C:36]=1[S:45]([C:48]([F:51])([F:50])[F:49])(=[O:47])=[O:46])[CH2:26][S:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCCl.ClC(Cl)C.C(Cl)Cl>[P:1]([O:13][CH2:14][CH2:15][N:16]1[CH2:17][CH2:18][N:19]([CH2:23][CH2:24][C@@H:25]([NH:34][C:35]2[CH:40]=[CH:39][C:38]([S:41](=[O:42])(=[O:43])[NH2:44])=[CH:37][C:36]=2[S:45]([C:48]([F:50])([F:49])[F:51])(=[O:47])=[O:46])[CH2:26][S:27][C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH2:20][CH2:21]1)([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:2]

参加物

8

反応物 4

HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 58080136Di-tert-butyl 2-(piperazin-1-yl)ethyl phosphate2 回HCID 86661872(R)-4-(4-oxo-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide2 回

生成物 1

HCID 66723554(R)-di-tert-butyl 2-(4-(4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butyl)piperazin-1-yl)ethyl phosphate収率 94.7%

試薬・触媒・溶媒 3

HCID 111,2-Dichloroethane溶媒HCID 6344Dichloromethane溶媒HCID 63651,1-Dichloroethane溶媒

実験手順

A solution of di-tert-butyl 2-(piperazin-1-yl)ethyl phosphate (INTERMEDIATE 60, 0.31 g, 0.95 mmol) in 1,2-dichloroethane (4 ml) was added to a solution of (R)-4-(4-oxo-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide (INTERMEDIATE 45, 0.46 g, 0.95 mmol) in dichloroethane (5.0 ml) at room temperature. The reaction mixture was allowed to stir for 15 minutes at r.t, and solid sodium triacetoxyborohydride (0.30 g, 1.43 mmol) was added. The mixture was stirred for 1 hour at ambient temperature. To the reaction mixture was added 0.5 N NaOH (10 ml) and DCM (20 ml). After stirring for 15 mins at r.t, the layers were separated and the organic layer was washed with NaHCO3 (saturated aq.) and brine, and dried (Na2SO4). The volatiles were removed under reduced pressure. Purification by column chromatography (ISCO, silica gel, eluting with 0→100% EtOAc/hexanes) gave the title compound (0.71 g, yield: 94%).

後処理

  1. additionwas added
  2. stirringAfter stirring for 15 mins at r.t
  3. customthe layers were separated
  4. washthe organic layer was washed with NaHCO3 (saturated aq.) and brine
  5. dry with materialdried (Na2SO4)
  6. customThe volatiles were removed under reduced pressure
  7. customPurification
  8. washby column chromatography (ISCO, silica gel, eluting with 0→100% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-0bca3c97ba6340d8b01d252bea7814b2
出典データセット
uspto-grants-2015_04
特許番号
US09018381B2

反応ノート

読み込み中…