Hydrochloric Acid → 4-(2-Butoxy-5-chlorobenzamidomethyl)-phenylacetic acid

HRID 1706471Notes

Reaction equation

HRID 1706471 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]([O:13]CC)=[O:12])=[CH:6][CH:5]=1.C(C1C=CC(CC(OCC)=O)=CC=1)#N.[CH2:30]([O:34][C:35]1[CH:43]=[CH:42][C:41]([Cl:44])=[CH:40][C:36]=1[C:37](Cl)=[O:38])[CH2:31][CH2:32][CH3:33].Cl.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.O.C(N(CC)CC)C>[CH2:30]([O:34][C:35]1[CH:43]=[CH:42][C:41]([Cl:44])=[CH:40][C:36]=1[C:37]([NH:2][CH2:3][C:4]1[CH:5]=[CH:6][C:7]([CH2:10][C:11]([OH:13])=[O:12])=[CH:8][CH:9]=1)=[O:38])[CH2:31][CH2:32][CH3:33]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 279718Ethyl 2-(4-cyanophenyl)acetateHCID 516892Sodium BicarbonateHCID 128632402-Butoxy-5-chlorobenzoyl chlorideHCID 19747408Ethyl 2-[4-(aminomethyl)phenyl]acetate hydrochloride

Product 1

HCID 234530434-(2-Butoxy-5-chlorobenzamidomethyl)-phenylacetic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolvent3×HCID 8471TriethylamineSolvent

Procedure

11.5 g Ethyl 4-aminomethylphenylacetate hydrochloride (m.p. 172° C.; prepared by the catalytic hydrogenation of ethyl 4-cyanophenylacetate) are suspended in 200 ml toluene. After the addition of 13.9 ml triethylamine, there is added dropwise, while cooling, a solution of 12.4 g 2-butoxy-5-chlorobenzoyl chloride in 10 ml toluene. The reaction mixture is subsequently heated under reflux for 2 hours, while stirring. After cooling, the toluene phase is treated successively with dilute hydrochloric acid, aqueous sodium bicarbonate solution and water and then evaporated. The evaporation residue is heated on a steambath with 2 N aqueous sodium hydroxide solution and the solution then filtered. The filtrate is acidified with dilute hydrochloric acid. The precipitated 4-(2-butoxy-5-chlorobenzamidomethyl)-phenylacetic acid is reprecipitated via its sodium salt and recrystallized from ethanol. The yield is 3.9 g (20% of theory); m.p. 198° C.

Workup

  1. additionis added dropwise
  2. temperaturewhile cooling
  3. temperatureThe reaction mixture is subsequently heated
  4. temperatureunder reflux for 2 hours
  5. temperatureAfter cooling
  6. customevaporated
  7. temperatureThe evaporation residue is heated on a steambath with 2 N aqueous sodium hydroxide solution
  8. filtrationthe solution then filtered
  9. customThe precipitated 4-(2-butoxy-5-chlorobenzamidomethyl)-phenylacetic acid is reprecipitated via its sodium salt
  10. customrecrystallized from ethanol

Sources & evidence

ORD record
ord-ed3dfca402d94e238ff6a83e45727b2a
Source dataset
uspto-grants-1980_06
Patent number
US04207341

Reaction notes

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