Hydrochloric Acid → 4-[[(1R)-3-(4-Morpholinyl)-1-[(phenylthio)methyl]propyl]amino]-3-[(trifluoromethyl)sulfonyl]benzenesulfonamide

HRID 1771200Notes

Reaction equation

HRID 1771200 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7](=O)[CH2:8][C@@H:9]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([S:25]([NH2:28])(=[O:27])=[O:26])=[CH:21][C:20]=2[S:29]([C:32]([F:35])([F:34])[F:33])(=[O:31])=[O:30])[CH2:10][S:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:3][CH2:2]1.B.C1COCC1.Cl.C([O-])([O-])=O.[Na+].[Na+]>CCOC(C)=O.CO>[O:1]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][C@@H:9]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([S:25]([NH2:28])(=[O:26])=[O:27])=[CH:21][C:20]=2[S:29]([C:32]([F:35])([F:33])[F:34])(=[O:31])=[O:30])[CH2:10][S:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 2723981Borane;tetrahydrofuranHCID 667238584-[[(1R)-3-(4-Morpholinyl)-3-oxo-1-[(phenylthio)methyl]propyl]amino]-3-trifluoromethylsulfonyl-benzenesulfonamide2×

Product 1

HCID 250584544-[[(1R)-3-(4-Morpholinyl)-1-[(phenylthio)methyl]propyl]amino]-3-[(trifluoromethyl)sulfonyl]benzenesulfonamideYield 68.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

(R)-4-(4-morpholino-4-oxo-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide (INTERMEDIATE 68, 2.01 g, 3.5 mmol) was dissolved in a solution of borane-THF complex (1M in THF, 8.0 ml, 8.0 mmol) and the resulting solution was stirred at room temperature overnight. The flask was opened to atmosphere and cautiously treated with MeOH (4.0 ml) followed by concentrated HCl (1.55 ml). The resulting mixture was heated at reflux for 3 hours and was then allowed to cool to room temperature. The pH of the mixture was adjusted to approximately 10 by the addition of aqueous solution of Na2CO3 (2 M) resulting in a precipitate. The mixture was dissolved in EtOAc (250 ml) and washed with water (125 ml), brine (125 ml), and dried (Na2SO4). Evaporation of the volatiles under reduced pressure afforded a concentrate, which was purified by column chromatography (ISCO, 80 g silica gel column, eluting with 0→100% EtOAc/hexanes) to provide the title product (1.33 g, yield: 68%).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for 3 hours
  3. temperatureto cool to room temperature
  4. customresulting in a precipitate
  5. washwashed with water (125 ml), brine (125 ml)
  6. dry with materialdried (Na2SO4)
  7. customEvaporation of the volatiles under reduced pressure
  8. customafforded a concentrate, which
  9. customwas purified by column chromatography (ISCO, 80 g silica gel column, eluting with 0→100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-0bbe5095cf9643d6a030ce5fe05b1bf1
Source dataset
uspto-grants-2016_02
Patent number
US09248140B2

Reaction notes

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