Triphenylphosphine → 4-Chloro-3-nitro-5-(2-oxo-4-(2,4,6-trimethoxybenzyl)piperazin-1-yl)benzonitrile

HRID 921871Notes

Reaction equation

HRID 921871 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[Cl:34][C:35]1[C:40]([N+:41]([O-:43])=[O:42])=[CH:39][C:38]([C:44]#[N:45])=[CH:37][C:36]=1[NH:46][C:47](=[O:66])[CH2:48][N:49]([CH2:63][CH2:64]O)[CH2:50][C:51]1[C:56]([O:57][CH3:58])=[CH:55][C:54]([O:59][CH3:60])=[CH:53][C:52]=1[O:61][CH3:62]>C1COCC1.CCOC(C)=O.O>[Cl:34][C:35]1[C:36]([N:46]2[CH2:64][CH2:63][N:49]([CH2:50][C:51]3[C:56]([O:57][CH3:58])=[CH:55][C:54]([O:59][CH3:60])=[CH:53][C:52]=3[O:61][CH3:62])[CH2:48][C:47]2=[O:66])=[CH:37][C:38]([C:44]#[N:45])=[CH:39][C:40]=1[N+:41]([O-:43])=[O:42]

Participants

7

Reactant 3

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 89922329N-(2-chloro-5-cyano-3-nitrophenyl)-2-((2-hydroxyethyl)(2,4,6-trimethoxybenzyl)amino)acetamide

Product 1

HCID 899225714-Chloro-3-nitro-5-(2-oxo-4-(2,4,6-trimethoxybenzyl)piperazin-1-yl)benzonitrileYield 19.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of triphenylphosphine (263 mg, 1.002 mmol) in THF (2 mL) was added DIAD (0.195 mL, 1.002 mmol). The reaction mixture was stirred for 10 min. Then a solution of N-(2-chloro-5-cyano-3-nitrophenyl)-2-((2-hydroxyethyl)(2,4,6-trimethoxybenzyl)amino)acetamide (160 mg, 0.334 mmol) in TIIF (1.000 mL) was added drop wise. The reaction mixture was then stirred at room temperature for 3 h. LC-MS indicated the desired peak. It was diluted with EtOAc and water. The aqueous layer was extracted with EtOAc and the combined organic layer was washed with water, brine, dried over Na2SO4, filtered and concentrated. Purification via silica gel chromatography (0-100% EtOAc in Hexanes, 12 g) gave 4-chloro-3-nitro-5-(2-oxo-4-(2,4,6-trimethoxybenzyl)piperazin-1-yl)benzonitrile (30 mg) as a yellow solid. TFA (1 mL) was added to the above obtained solution of 4-chloro-3-nitro-5-(2-oxo-4-(2,4,6-trimethoxybenzyl)piperazin-1-yl)benzonitrile (30 mg, 0.065 mmol) and ANISOLE (0.028 mL, 0.260 mmol) in DCM (1 mL) and the reaction mixture was stirred at room temperature for 2 h. LC-MS showed completion. Solvent was evaporated and purification via flash chromatography (0-10% MeOH in DCM, 24 g) gave 4-chloro-3-nitro-5-(2-oxopiperazin-1-yl)benzonitrile (20 mg) as a yellow oil.

Workup

  1. stirringThe reaction mixture was then stirred at room temperature for 3 h
  2. extractionThe aqueous layer was extracted with EtOAc
  3. washthe combined organic layer was washed with water, brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification via silica gel chromatography (0-100% EtOAc in Hexanes, 12 g)

Sources & evidence

ORD record
ord-61e306e2fd6a4d7d8f23872da263398e
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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