Hydrochloric Acid → Phenyl-o-methylphenylamino-acetic acid hydrochloride

HRID 76981

Reaction equation

HRID 76981 reaction equation
Br[CH:2]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:3]([O:5]CC)=[O:4].[NH2:14][C:15]1[C:16]([CH3:21])=[CH:17][CH:18]=[CH:19][CH:20]=1.CCN(C(C)C)C(C)C.O.[OH-].[Li+].[ClH:34]>C(#N)C.O1CCOCC1.O>[ClH:34].[C:8]1([CH:2]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH3:21])[C:3]([OH:5])=[O:4])[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 7242O-ToluidineHCID 81531DiisopropylethylamineHCID 97780Ethyl bromophenylacetateHCID 168937Lithium hydroxide, monohydrate

Product 1

HCID 67124826Phenyl-o-methylphenylamino-acetic acid hydrochlorideYield 63%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Ethyl 2-bromo-2-phenylacetate (0.28 mL, 1.64 mmol), ortho-toluidine (0.26 mL, 2.47 mmol) and DIPEA (0.43 mL, 2.47 mmol) are dissolved in acetonitrile (5 mL) and stirred under MW irradiation at 100° C. for 1 hour (Conversion complete by UPLC/MS-UV). Lithium hydroxide hydrate (207 mg, 4.94 mmol) and water (3 mL) are added and the mixture is stirred at RT for 16 hours. 4M HCl in dioxane is added until pH is about 1, then the solvents are evaporated, the residue is suspended in water, sonicated, cooled at 0° C. and the resulting solid is recovered by filtration and dried under vacuum to get intermediate I86 as a off-white solid (290 mg, 63% yield).

Workup

  1. stirringthe mixture is stirred at RT for 16 hours
  2. customthe solvents are evaporated
  3. customsonicated
  4. temperaturecooled at 0° C.
  5. filtrationthe resulting solid is recovered by filtration
  6. customdried under vacuum

Sources & evidence

ORD record
ord-99cdd32759ab4cd194d408358df71df5
Source dataset
uspto-grants-2014_09
Patent number
US08835682B2

Linked notes

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