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

HRID 1476288Notes

Reaction equation

HRID 1476288 reaction equation
[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]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 58080210Di-tert-butyl 2-(ethylamino)ethyl phosphate2×HCID 86661872(R)-4-(4-oxo-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide2×

Product 1

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

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 6344DichloromethaneSolvent

Procedure

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%).

Workup

  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)

Sources & evidence

ORD record
ord-b7a6865c071b4ec5a30407c5866cc2c0
Source dataset
uspto-grants-2015_04
Patent number
US09018381B2

Reaction notes

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