Sodium triacetoxyborohydride → (R)-4-(4-((2-(tert-butyldimethylsilyloxy)ethyl)(ethyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide

HRID 1476299Notes

Reaction equation

HRID 1476299 reaction equation
O=[CH:2][CH2:3][C@@H:4]([NH:13][C:14]1[CH:19]=[CH:18][C:17]([S:20]([NH2:23])(=[O:22])=[O:21])=[CH:16][C:15]=1[S:24]([C:27]([F:30])([F:29])[F:28])(=[O:26])=[O:25])[CH2:5][S:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[Si:31]([O:38][CH2:39][CH2:40][NH:41][CH2:42][CH3:43])([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[Si:31]([O:38][CH2:39][CH2:40][N:41]([CH2:42][CH3:43])[CH2:2][CH2:3][C@@H:4]([NH:13][C:14]1[CH:19]=[CH:18][C:17]([S:20]([NH2:23])(=[O:22])=[O:21])=[CH:16][C:15]=1[S:24]([C:27]([F:29])([F:30])[F:28])(=[O:26])=[O:25])[CH2:5][S:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32]

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 72666539[2-(tert-Butyldimethylsilanyloxy)ethyl]ethylamine2×HCID 86661872(R)-4-(4-oxo-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide2×

Product 1

HCID 66723826(R)-4-(4-((2-(tert-butyldimethylsilyloxy)ethyl)(ethyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamideYield 62%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of (R)-4-(4-oxo-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide (INTERMEDIATE 45, 3.98 g, 8.25 mmol) and 2-(tert-butyldimethylsilyloxy)-N-ethylethanamine (INTERMEDIATE 63, 1.68 g, 8.25 mmol) in 1,2-dichloroethane (27.5 ml) was added sodium triacetoxyborohydride (2.62 g, 12.37 mmol). The resulting mixture was stirred in the dark for 11.5 h and was then quenched with 0.5 M aqueous sodium hydroxide (50 ml). After vigorous stirring for 10 min, the opaque mixture became clear. The layers were diluted with ethyl acetate and then separated. The organic layer was washed with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride before being dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (ISCO, 330 g SiO2, 50→100% ethyl acetate in hexanes for 20 mins then 0→20% methanol in ethyl acetate for 20 mins followed by 0→20% methanol in ethyl acetate over 20 min) to afford the title product (3.41 g, yield: 62%).

Workup

  1. customwas then quenched with 0.5 M aqueous sodium hydroxide (50 ml)
  2. stirringAfter vigorous stirring for 10 min
  3. additionThe layers were diluted with ethyl acetate
  4. customseparated
  5. washThe organic layer was washed with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride
  6. dry with materialbefore being dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by column chromatography (ISCO, 330 g SiO2, 50→100% ethyl acetate in hexanes for 20 mins
  10. wait0→20% methanol in ethyl acetate for 20 mins followed by 0→20% methanol in ethyl acetate over 20 min

Sources & evidence

ORD record
ord-bf0ee3e4ac374d568089247606f131a0
Source dataset
uspto-grants-2015_04
Patent number
US09018381B2

Reaction notes

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