Hydrogen Peroxide → HCID 118276615, compound

HRID 1053668Notes

Reaction equation

HRID 1053668 reaction equation
C(OO)(=[O:3])C.OO.C(OC(=O)C)(=O)C.[Cl:15][CH2:16][CH2:17][N:18]([CH2:44][CH2:45][Cl:46])[C:19]1[CH:20]=[CH:21][C:22]([CH3:43])=[C:23]([CH2:25][C@@H:26]([NH:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH:24]=1>ClCCl>[C:31]([O:30][C:28](=[O:29])[CH2:27][C@H:26]([NH:35][C:36]([O:38][C:39]([CH3:40])([CH3:42])[CH3:41])=[O:37])[CH2:25][C:23]1[CH:24]=[C:19]([N+:18]([O-:3])([CH2:44][CH2:45][Cl:46])[CH2:17][CH2:16][Cl:15])[CH:20]=[CH:21][C:22]=1[CH3:43])([CH3:34])([CH3:33])[CH3:32]

Participants

6

Reactant 4

HCID 784Hydrogen PeroxideHCID 6585Peracetic AcidHCID 7918Acetic AnhydrideHCID 118276572HCID 118276572, compound

Product 1

HCID 118276615HCID 118276615, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Adapting literature known protocols (Tercel, et al., J. Med. Chem. 1995, 38, 1247-1252; and Kirkpatrick, et al., U.S. Pat. No. 7,399,785), peracetic acid (H3CCO3H) is freshly prepared by adding hydrogen peroxide (H2O2) (1.5 mL of a 35 wt-% aqueous solution, 14.0 mmol) dropwise to acetic anhydride (Ac2O) (1.52 mL, 1.65 g, 16.0 mmol). When the reaction mixture is homogeneous, a solution of tert-butyl(3R)-4-[5-[bis(2-chloroethyl)amino]-2-methyl-phenyl]-3-(tert-butoxycarbonylamino)butanoate (6e) (1.61 g, 3.29 mmol) in dichloromethane (DCM) (20 mL) is added with vigorous stirring at about room temperature for about 2 h. The reaction is followed by TLC and/or LC/MS to completion. The reaction is quenched with 2.0 N hydrochloric acid (HCl), and the aqueous layer separated and repeatedly washed with DCM to the organic extracts are colorless. The aqueous phase is evaporated to dryness under reduced pressure, dried over anhydrous sodium sulfate (Na2SO4), and partially reduced in volume. Diethyl ether (Et2O) is added to separate the title compound 3-[(2R)-4-tert-butoxy-2-(tert-butoxycarbonylamino)-4-oxo-butyl]-N,N-bis(2-chloroethyl)-4-methyl-benzeneamine oxide (22a). The material may be purified by silica gel column chromatography.

Workup

  1. customThe reaction is quenched with 2.0 N hydrochloric acid (HCl)
  2. customthe aqueous layer separated
  3. washrepeatedly washed with DCM to the organic extracts
  4. customThe aqueous phase is evaporated to dryness under reduced pressure
  5. dry with materialdried over anhydrous sodium sulfate (Na2SO4)
  6. additionDiethyl ether (Et2O) is added
  7. customto separate the title compound 3-[(2R)-4-tert-butoxy-2-(tert-butoxycarbonylamino)-4-oxo-butyl]-N,N-bis(2-chloroethyl)-4-methyl-benzeneamine oxide (22a)
  8. customThe material may be purified by silica gel column chromatography

Sources & evidence

ORD record
ord-975af8a54ed14ec2845e511630e944a0
Source dataset
uspto-grants-2016_07
Patent number
US09394237B2

Reaction notes

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