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

HRID 1771193Notes

Reaction equation

HRID 1771193 reaction equation
[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]

Participants

8

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent

Procedure

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%).

Workup

  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)

Sources & evidence

ORD record
ord-0d849dd7066e487e8011984995dd8e4d
Source dataset
uspto-grants-2016_02
Patent number
US09248140B2

Reaction notes

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