Sodium Thiosulfate → (R)-tert-butyl 2-isopropyl-4-(4-(methoxycarbonyl)-5-(methylsulfonyl)-2-nitrophenyl)-3-oxopiperazine-1-carboxylate

HRID 1468889Notes

Reaction equation

HRID 1468889 reaction equation
[CH:1]([C@@H:4]1[C:9](=[O:10])[N:8]([C:11]2[CH:16]=[C:15](SC)[C:14]([C:19]([O:21][CH3:22])=[O:20])=[CH:13][C:12]=2[N+:23]([O-:25])=[O:24])[CH2:7][CH2:6][N:5]1[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])([CH3:3])[CH3:2].[CH:33]1C=C(Cl)C=C(C(OO)=O)C=1.[O-:44][S:45]([O-:48])(=S)=O.[Na+].[Na+]>C(Cl)Cl>[CH:1]([C@@H:4]1[C:9](=[O:10])[N:8]([C:11]2[CH:16]=[C:15]([S:45]([CH3:33])(=[O:48])=[O:44])[C:14]([C:19]([O:21][CH3:22])=[O:20])=[CH:13][C:12]=2[N+:23]([O-:25])=[O:24])[CH2:7][CH2:6][N:5]1[C:26]([O:28][C:29]([CH3:32])([CH3:30])[CH3:31])=[O:27])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 24477Sodium ThiosulfateHCID 70297m-Chloroperbenzoic acidHCID 89814992(R)-tert-butyl 2-isopropyl-4-(4-(methoxycarbonyl)-5-(methylthio)-2-nitrophenyl)-3-oxopiperazine-1-carboxylate

Product 1

HCID 89827918(R)-tert-butyl 2-isopropyl-4-(4-(methoxycarbonyl)-5-(methylsulfonyl)-2-nitrophenyl)-3-oxopiperazine-1-carboxylateYield 85.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a 2 L round-bottom flask containing (R)-tert-butyl 2-isopropyl-4-(4-(methoxycarbonyl)-5-(methylthio)-2-nitrophenyl)-3-oxopiperazine-1-carboxylate (crude 91.7 g, 0.196 mol) in CH2Cl2 (1 L) was added m-CPBA (84.6 g, 0.49 mmol, 2.5 eq). The mixture was stirred at rt overnight. Sat. Na2S2O3 solution was added slowly to quench the reaction. The mixture was extracted with CH2Cl2 (4×3 L). The combined organic layers were washed successively with Na2S2O3 solution (500 mL), NaHCO3 solution (500 mL) and brine, dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The residue was purified by column chromatography on silica gel eluting with dichloromethane to give (R)-tert-butyl 2-isopropyl-4-(4-(methoxycarbonyl)-5-(methylsulfonyl)-2-nitrophenyl)-3-oxopiperazine-1-carboxylate (83.7 g, 85.4% yield) as a yellow solid. LC-MS MS (ESI) m/z 444.0 [M−56+H]+, 522.1 [M+Na]+. 1H NMR (CDCl3 300 MHz): δ 8.29 (s, 1H), 8.12 (s, 1H), 4.61-4.17 (m, 2H), 4.00-3.94 (m, 4H), 3.70-3.60 (m, 1H), 3.51-3.43 (m, 4H), 2.39-2.32 (m, 1H), 1.50 (s, 9H), 1.07 (d, J=6.9 Hz, 3H), 1.01 (d, J=6.9 Hz, 3H).

Workup

  1. customto quench
  2. customthe reaction
  3. extractionThe mixture was extracted with CH2Cl2 (4×3 L)
  4. washThe combined organic layers were washed successively with Na2S2O3 solution (500 mL), NaHCO3 solution (500 mL) and brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-a65ccc2356c2489ebc70cea4ad0338ae
Source dataset
uspto-grants-2015_04
Patent number
US09006244B2

Reaction notes

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