(-)-Mandelic acid → (R)-2-Hydroxy-N-(4-nitrophenethyl)-2-phenylacetamide

HRID 76022Notes

Reaction equation

HRID 76022 reaction equation
Cl.[N+:2]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH2:12][NH2:13])=[CH:7][CH:6]=1)([O-:4])=[O:3].[C:14](O)(=[O:23])[C@@H:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[OH:16].OC1C2N=NNC=2C=CC=1.Cl.CN(C)CCCN=C=NCC>O.Cl.CN(C)CCCN=C=NCC.CN(C)C=O.C(N(CC)CC)C>[OH:16][C@H:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:14]([NH:13][CH2:12][CH2:11][C:8]1[CH:7]=[CH:6][C:5]([N+:2]([O-:4])=[O:3])=[CH:10][CH:9]=1)=[O:23]

Participants

9

Reactant 4

HCID 11914(-)-Mandelic acidHCID 458983Benzeneethanamine, 4-nitro-, hydrochloride (1:1)HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178418300HCID 178418300, compound

Product 1

HCID 59678380(R)-2-Hydroxy-N-(4-nitrophenethyl)-2-phenylacetamideYield 87.6%

Reagents, catalysts & solvents 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
87 °C

Procedure

To a mixture of 5.90 kg of 4-nitrophenylethylamine monohydrochloride, 4.43 kg of (R)-mandelic acid, 2.94 kg of triethylamine and 22 liters of N,N-dimethylformamide were added 3.93 kg of hydroxybenztriazole and 5.58 kg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide monohydrochloride (EDC) followed by stirring at about room temperature for 2 hours. EDC (0.28 kg) was further added thereto and the mixture was stirred at about room temperature throughout one night. The reaction solution was diluted with 110 liters of water and extracted with ethyl acetate (60 liters, 30 liters). The organic layer was successively washed with 60 liters of 1 M aqueous hydrochloric acid, 60 liters of 20% aqueous solution of potassium carbonate and water (60 liters, 60 liters) and concentrated in vacuo at 10 to 19° C. The residue was dissolved in 35 liters of toluene with heating at 87° C., cooled and stirred at 20° C. throughout one night. The resulting crystals were filtered and washed with 10 liters of toluene. This was dried in vacuo to give 7.66 kg of (R)-2-hydroxy-N-[2-(4-nitrophenyl)ethyl]-2-phenylacetamide as light yellow crystals.

Workup

  1. stirringthe mixture was stirred at about room temperature throughout one night
  2. extractionextracted with ethyl acetate (60 liters, 30 liters)
  3. washThe organic layer was successively washed with 60 liters of 1 M aqueous hydrochloric acid, 60 liters of 20% aqueous solution of potassium carbonate and water (60 liters, 60 liters)
  4. concentrationconcentrated in vacuo at 10 to 19° C
  5. dissolutionThe residue was dissolved in 35 liters of toluene
  6. temperaturecooled
  7. stirringstirred at 20° C. throughout one night
  8. filtrationThe resulting crystals were filtered
  9. washwashed with 10 liters of toluene
  10. customThis was dried in vacuo

Sources & evidence

ORD record
ord-69cdc97cad39470e9e3502df895a0fae
Source dataset
uspto-grants-2014_09
Patent number
US08835474B2

Reaction notes

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