Hydroxyphenylacetic acid → 3-[((4-Chloroanilino)carbonyl)methyl]phenol

HRID 1489177Notes

Reaction equation

HRID 1489177 reaction equation
[CH3:1][C:2]([CH3:4])=[O:3].[OH:5][C:6]1C=[CH:10][C:9](CC(O)=O)=[CH:8][CH:7]=1.[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[CH:19][CH:18]=1.P(Cl)(Cl)(Cl)(Cl)Cl>C1(C)C=C(C)C=C(C)C=1.C(C(CC)=O)C>[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH:21][C:6]([CH2:7][C:8]2[CH:1]=[C:2]([OH:3])[CH:4]=[CH:10][CH:9]=2)=[O:5])=[CH:19][CH:18]=1

Participants

7

Reactant 4

HCID 127Hydroxyphenylacetic acidHCID 180AcetoneHCID 78124-ChloroanilineHCID 24819Phosphorus pentachloride

Product 1

HCID 234407563-[((4-Chloroanilino)carbonyl)methyl]phenolYield 99%

Reagents, catalysts & solvents 2

HCID 7288Ethyl ketoneSolventHCID 7947MesityleneSolvent

Procedure

FIG. 6b presents a similar reaction scheme to FIG. 6a, except that 3- rather than 4-hydroxyphenylacetic acid (HPAA) is used as the precursor material so that the final compound has a meta rather than a pare substitution. In addition, rather than reacting with acetone (dimethyl ketone) a diethyl ketone is used to position ethyl, rather than methyl, moieties in the group substituted on one of the phenyl rings. By example, 1.5 g (10 mmol) 3-HPAA and 2.6 g (20 mmol) 4-chloroaniline in 20 ml of mesitylene was heated to reflux. Then 0.33 g (2.55 mmol) PCl5 was then slowly added to the above refluxing solution and the refluxing was continued for two hours. The reaction mixture was then cooled and then worked up as described above to yield 2.2 g (99% yield) of 3-[((4-chloroanilino) carbonyl)methyl]phenol. As described above, chloroform (0.8 ml) was added to a stirred and ice-cooled mixture of 1.23 grams of 3-[((4-chloroanilino) carbonyl)methyl]phenol and 1.6 g NaOH in 15 ml of acetone. The reaction mixture was allowed to warm to room temperature and stirring continued for an additional 10 hours. The usual work-up yielded 2-[3-(((4-chloroanalino)carbonyl) methyl)]phenoxy!-2-methylpropionic acid as a low temperature melting sticky solid (C,H,Cl,N analysis yielded (C18H18ClNO4); NMR δPPM: 1.42 (6 H, s, CH3), 3.61 (2 H, s, benzylic CH2), and 6.6-7.75 (8 H, m, aromatic H)). However, rather than using acetone as the reaction solvent, diethylketone can be used in the same manner as described above to yield the butanoic acid (as opposed to propanoic acid) structure shown in FIG. 6b.

Workup

  1. temperatureThe reaction mixture was then cooled

Sources & evidence

ORD record
ord-f532a97fd3d240a293ce7d6206194708
Source dataset
uspto-grants-1997_10
Patent number
US05677330

Reaction notes

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