Chloride → 2-(6-Methoxynaphthalen-2-yl)propanoyl chloride

HRID 1582843Notes

Reaction equation

HRID 1582843 reaction equation
[Cl-:1].[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[CH:10]=[C:9]([C@H:14]([CH3:18])[C:15](O)=[O:16])[CH:8]=[CH:7]2>ClCCl>[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[CH:10]=[C:9]([C@H:14]([CH3:18])[C:15]([Cl:1])=[O:16])[CH:8]=[CH:7]2

Participants

4

Reactant 2

HCID 312ChlorideHCID 156391Naproxen

Product 1

HCID 54916922-(6-Methoxynaphthalen-2-yl)propanoyl chloride

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2.85 ml, 32.5 mmol Oxaly chloride ((COCl)2) is added slowly to 3 g, 13 mmol (S)-2-(6-methoxy-2-naphthyl)propionic acid dissolved in 3 ml dichloromethane (CH2Cl2), and the resulting solution is heated under a first reflux temperature with stirring for 2 hours. The excess oxaly chloride is removed by evaporation under reduced pressure to obtain a crude product of (S)-2-(6-methoxy-2-naphthyl)propionic acid chloride. The crude (S)-2-(6-methoxy-2-naphthyl)propionic acid chloride is dissolved in 5 ml dichloromethane and then added to a solution of 3.36 ml, 32.5 mmol N,N′-diethylamine (HN(CH2CH3)2) and 5 ml triethylamine (TEA) in 10 ml dichloromethane with stirring under ice bath, i.e. under a temperature about 0° C. After some solids are produced, the mixture is stayed in a refrigerator overnight, i.e. stayed in a low temperature about−5° C. for a period of time about 12 hour. The mixture is evaporated to dryness under reduced pressure and the residue is purified by column chromatography over silica gel (70˜230 mesh ASTM) using dichloromethane/ethyl acetate (V:V=8:2) as the eluant. As a result, about 70 percent yield of white N,N′-diethyl (S)-2-(6-methoxy-2-naphthyl)propionate is obtained, which is the first intermediate (I) for synthesizing the chiral compound of the first preferred embodiment of the present invention.

Workup

  1. temperaturethe resulting solution is heated under a first reflux temperature
  2. customThe excess oxaly chloride is removed by evaporation under reduced pressure

Sources & evidence

ORD record
ord-216f3ae011364223bec11e4bb5aed99e
Source dataset
uspto-grants-2004_05
Patent number
US06740256B1

Reaction notes

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