Hydrochloric Acid → 2-(Phenylamino)propanoic acid

HRID 900633Notes

Reaction equation

HRID 900633 reaction equation
[NH2:1][C@H:2]([C:4]([OH:6])=[O:5])[CH3:3].I[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C([O-])([O-])=O.[K+].[K+].Cl>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.CN(C=O)C.C(OCC)(=O)C.O.CC1C(P(C2C(C)=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC1C(P(C2C(C)=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.Cl[Pd]Cl.[Cu]I.CCCCCC.C(OCC)(=O)C.C(O)(=O)C.C(N(CC)CC)C>[C:8]1([NH:1][CH:2]([CH3:3])[C:4]([OH:6])=[O:5])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

13

Reactant 4

HCID 313Hydrochloric AcidHCID 5950L-AlanineHCID 11430Potassium CarbonateHCID 11575Iodobenzene

Product 1

HCID 27603572-(Phenylamino)propanoic acidYield 45.4%

Reagents, catalysts & solvents 8

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 66133Benzyl triethylammonium chlorideCatalystHCID 10876480Bis(tri-o-tolylphosphine)palladium(II) DichlorideCatalystHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolventHCID 21901998Ethyl acetate hexane acetic acidSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of alanine (356 mg, 4.0 mmol), iodobenzene (816 mg, 4.0 mmol), trans-dichlorobis(tri-o-tolylphosphine)palladium(II) {Pd[P(o-Tol)3]2Cl2} (160 mg, 0.2 mmol), copper(I) iodide (40 mg, 0.2 mmol), K2CO3 (552 mg, 4.0 mmol), benzyltriethylammonium chloride (160 mg, 0.8 mmol), triethylamine (1.6 mL) and water (0.8 mL) in DMF (8 mL) was stirred under nitrogen atmosphere at 100° C. for 20 hours. The mixture was cooled to room temperature, diluted with ethyl acetate (50 mL) and water (50 mL), acidified with 6N HCl to the pH=2 to 3. The aqueous layer was extracted with ethyl acetate (50 mL×4). The combined organic layers were washed with water, brine, dried over anhydrous Na2SO4, filtered and evaporated in vacuo to give a red oil. Flash chromatography using hexane/ethyl acetate/acetic acid (95/5/0.5 to 80/20/0.5) to afford 300 mg (45% yield) of the title compound as a pink solid. 1H-NMR (500 MHz, CDCl3/CD3OD=0.5 ml/3 drops) δ 1.45 (d, 3H), 4.02-4.15 (m, H), 6.57-6.70 (m, 3H), 7.11-7.25 (m, 2H); Analytical HPLC: 6.10 min. LC-MS: m/e=166 (M+H+).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionThe aqueous layer was extracted with ethyl acetate (50 mL×4)
  3. washThe combined organic layers were washed with water, brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customto give a red oil

Sources & evidence

ORD record
ord-f521e4f4c0254f28b604189a0262906d
Source dataset
uspto-grants-2008_04
Patent number
US07358273B2

Reaction notes

Loading…