Water → 4-Acetamidophenyl 4-nitrophenyl carbonate

HRID 571161Notes

Reaction equation

HRID 571161 reaction equation
N1C=CC=CC=1.[OH:7][C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15](=[O:17])[CH3:16])=[CH:10][CH:9]=1.[C:18](Cl)(=[O:29])[O:19][C:20]1[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=1.O>ClCCl>[C:18](=[O:29])([O:19][C:20]1[CH:21]=[CH:22][C:23]([N+:26]([O-:28])=[O:27])=[CH:24][CH:25]=1)[O:7][C:8]1[CH:9]=[CH:10][C:11]([NH:14][C:15](=[O:17])[CH3:16])=[CH:12][CH:13]=1

Participants

6

Reactant 4

HCID 962WaterHCID 1049PyridineHCID 1983Acetaminophen3×HCID 821294-Nitrophenyl chloroformate

Product 1

HCID 594879154-Acetamidophenyl 4-nitrophenyl carbonateYield 47%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Adapting a known procedure (P. Pasetto, et al., Anal. Chim. Acta, 2005, 542(1), 66-75), 8.03 mL of anhydrous pyridine (7.84 g, 99.3 mmol; 1.5 eq.) was added at a temperature of about 0° C. (ice bath) to a suspension of 10.00 g N-(4-hydroxyphenyl)acetamide (1) (paracetamol (INN), acetaminophen (USAN) (66.2 mmol; 1.0 eq.) in 300 mL of anhydrous dichloromethane (DCM). The reaction mixture was stirred at the same temperature for about 10 minutes. To this mixture, a solution of 13.97 g (69.5 mmol; 1.05 eq.) of commercially available 4-nitrophenyl carbonochloridate (2) in 20 mL of anhydrous DCM was then added dropwise and the reaction mixture was stirred with gradual warming to room temperature for overnight. Fifty (50) mL of water were added to the reaction mixture. A solid precipitated out of solution. The solid was filtered off and washed successively with diethylether (Et2O) (2×50 mL) and hexane (4×50 mL) to afford 9.92 g (47% yield) of the target compound 3 as a colorless solid after drying in high vacuum. The initial filtrate (DCM and water) was washed with a saturated aqueous solution of sodium chloride (NaCl/brine). The organic layer was dried using anhydrous sodium sulfate (Na2SO4) to afford an additional 7.0 g (33% yield) of the target compound 3. Rf-value: 0.35 (ethyl acetate/hexane=1:1). 1H NMR (DMSO-d6, 300 MHz): δ=10.09 (s, 1H), 8.34 (d, J=9.3 Hz, 2H), 7.68 (d, J=9.3 Hz, 2H), 7.64 (d, J=9.0 Hz, 2H), 7.31 (d, J=8.7 Hz, 2H), 2.05 (s, 3H) ppm. LC/MS (ESI): m/z=317.2 [M+H]+. The analytical data corresponded to the analytical data given in the literature.

Workup

  1. stirringthe reaction mixture was stirred
  2. customA solid precipitated out of solution
  3. filtrationThe solid was filtered off
  4. washwashed successively with diethylether (Et2O) (2×50 mL) and hexane (4×50 mL)

Sources & evidence

ORD record
ord-ea36f0d8afae49d78d0748c6592de10e
Source dataset
uspto-grants-2015_05
Patent number
US09024055B2

Reaction notes

Loading…