4-Nitrophenol → 4-Nitrophenyl 2-chloro-5-(pivalamidomethyl)benzoate

HRID 1469742Notes

Reaction equation

HRID 1469742 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([CH2:11][NH:12][C:13](=[O:18])[C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].CCN=C=NCCCN(C)C.[CH:30]1[C:35]([N+:36]([O-:38])=[O:37])=[CH:34][CH:33]=[C:32](O)[CH:31]=1.CCN(C(C)C)C(C)C>C1COCC1.O>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([CH2:11][NH:12][C:13](=[O:18])[C:14]([CH3:15])([CH3:17])[CH3:16])=[CH:7][C:3]=1[C:4]([O:6][C:32]1[CH:31]=[CH:30][C:35]([N+:36]([O-:38])=[O:37])=[CH:34][CH:33]=1)=[O:5]

Participants

7

Reactant 4

HCID 9804-NitrophenolHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 584832082-Chloro-5-[(2,2-dimethylpropanamido)methyl]benzoic acid

Product 1

HCID 866922384-Nitrophenyl 2-chloro-5-(pivalamidomethyl)benzoateYield 51.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-chloro-5-(pivalamidomethyl)benzoic acid (Intermediate-5, 300 mg, 1.12 mmol) in THF (5 mL) were added EDCI (210 mg, 1.09 mmol), p-nitrophenol (154 mg, 1.10 mmol) and DIPEA (558 mg, 4.39 mmol) and the reaction mixture was stirred at rt for 4 h. Then water was added to the reaction mixture and it was extracted with EtOAc. The organic layer was washed with brine, separated, dried, filtered and concentrated. The residue was purified by column chromatography to afford 222 mg of the title product. 1H NMR (300 MHz, DMSO d6): δ 8.36 (d, J=9.0 Hz, 2H), 8.20 (t, 1H), 7.97 (s, 1H), 7.62-7.59 (m, 3H), 7.51 (d, J=8.1 Hz, 1H), 4.30 (d, J=6.0 Hz, 2H), 1.11 (s, 9H).

Workup

  1. extractionwas extracted with EtOAc
  2. washThe organic layer was washed with brine
  3. customseparated
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-6bb05300c02f40ada61cb67ca33ec74a
Source dataset
uspto-grants-2015_04
Patent number
US09006257B2

Reaction notes

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