Oxalyl chloride → HCID 20546914, compound

HRID 2059300Notes

Reaction equation

HRID 2059300 reaction equation
[CH3:1][N:2]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[CH2:18][CH2:19][C:20](O)=[O:21])[C:3](=[O:11])[C:4]1[CH:9]=[CH:8][C:7]([Cl:10])=[CH:6][CH:5]=1.C(Cl)(=O)C(Cl)=O>C1(C)C=CC=CC=1>[CH3:1][N:2]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[CH2:18][CH2:19][CH2:20][OH:21])[C:3](=[O:11])[C:4]1[CH:5]=[CH:6][C:7]([Cl:10])=[CH:8][CH:9]=1

Participants

4

Reactant 2

HCID 65578Oxalyl chlorideHCID 12782128HCID 12782128, compound

Product 1

HCID 20546914HCID 20546914, compoundYield 78.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

15.8 g of 3-[2-(N-methyl-4-chlorobenzamido)-phenyl]-propionic acid and 15 g of oxalyl chloride are stirred in toluene for 2 hours. After following evaporation in vacuo, the residue is taken up in 60 ml of dioxane and added dropwise to 1.6 g of sodium borohydride in 40 ml of dioxane. Heating to 100° is effected for 4 hours, followed by addition of 2 N hydrochloric acid in an ice bath to the end of the gas development. Extraction with diethyl ether yields 11.9 g of 3-[2-(N-methyl-4-chlorobenzamido)-phenyl]-propanol as oil, which is reacted without further purification in 80 ml of toluene with 3 g of pyridine and 6 g of tosyl chloride to the 3-[2-(N-methyl-4-chlorobenzamido)-phenyl]-propyl-tosylate (33 hours of stirring at room temperature). The chromatographic purification (silica gel, eluent methylene chloride) yields 6.1 g (31% of theory). This tosylate in 70 ml of ethanol is added dropwise to a solution of 0.35 g of sodium and 3.2 g of diethyl malonate in 60 ml of ethanol. Following heating under reflux for 24 hours, working up by extraction with methylene chloride and chromatographic purification with silica gel/chloroform yield 5.4 g (89% of theory) of diethyl-3-[2-N-methyl-4-chlorobenzamido)-phenyl]-propyl malonate as oil, which is used under (a).

Workup

  1. customevaporation in vacuo
  2. additionadded dropwise to 1.6 g of sodium borohydride in 40 ml of dioxane
  3. temperatureHeating to 100°
  4. additionfollowed by addition of 2 N hydrochloric acid in an ice bath to the end of the gas development
  5. extractionExtraction with diethyl ether

Sources & evidence

ORD record
ord-35f0a1bca52c40e49ffe106165117588
Source dataset
uspto-grants-1982_03
Patent number
US04322439

Reaction notes

Loading…