Chlorambucil → Methyl 4-[4-[bis(2-chloroethyl)amino]phenyl]butanoate

HRID 1053596Notes

Reaction equation

HRID 1053596 reaction equation
[CH:1]1[C:6]([CH2:7][CH2:8][CH2:9][C:10]([OH:12])=[O:11])=[CH:5][CH:4]=[C:3]([N:13]([CH2:17][CH2:18][Cl:19])[CH2:14][CH2:15][Cl:16])[CH:2]=1.[CH:20](N(CC)C(C)C)(C)C>CO>[Cl:19][CH2:18][CH2:17][N:13]([CH2:14][CH2:15][Cl:16])[C:3]1[CH:2]=[CH:1][C:6]([CH2:7][CH2:8][CH2:9][C:10]([O:12][CH3:20])=[O:11])=[CH:5][CH:4]=1

Participants

4

Reactant 2

HCID 2708ChlorambucilHCID 81531Diisopropylethylamine

Product 1

HCID 20702730Methyl 4-[4-[bis(2-chloroethyl)amino]phenyl]butanoateYield 55%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of chlorambucil (600 mg, 2 mmol), HBTO (625 mg, 2 mmol), and N,N-diisopropylethylamine (300 uL, 2 mmol) was stirred in methanol at 55° C. for 18 hrs. After cooling to room temperature, the solvent was evaporated and the residue was quenched with 50 mL water. The mixture was then extracted with EtOAc and the combined organic layer was washed with water, then brine, and dried over Na2SO4. The solvent was evaporated and the residue was purified by silica gel column chromatography with hexane/CH2Cl2 (10:1) to provide the compound 27a (350 mg, 1.1 mmol, 55% yield) as a yellow oil. 1H NMR (400 MHz, Chloroform-d) δ 7.20-7.05 (dd, 2H), 6.71-6.62 (dd, 2H), 3.75-3.70 (m, 4H), 3.69 (s, 3H), 3.64 (m, 4H), 2.58 (t, J=7.6 Hz, 2H), 2.35 (t, J=7.5 Hz, 2H), 1.93 (p, J=7.6 Hz, 2H). HRMS (ESI, positive) m/z calcd. for C15H22Cl2NO2 [M+H]+: 318.10221, found: 318.10216.

Workup

  1. customthe solvent was evaporated
  2. customthe residue was quenched with 50 mL water
  3. extractionThe mixture was then extracted with EtOAc
  4. washthe combined organic layer was washed with water
  5. dry with materialbrine, and dried over Na2SO4
  6. customThe solvent was evaporated
  7. customthe residue was purified by silica gel column chromatography with hexane/CH2Cl2 (10:1)

Sources & evidence

ORD record
ord-43670aeb390a46ef919b0c031f9b3297
Source dataset
uspto-grants-2016_07
Patent number
US09394233B2

Reaction notes

Loading…