Chloride → 3-Phenyl-2-(phenylamino)propanoic acid

HRID 76972Notes

Reaction equation

HRID 76972 reaction equation
[NH2:1][C@@H:2]([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:3]([OH:5])=[O:4].I[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C([O-])([O-])=O.[K+].[K+].[Cl-].C(N(CC)CC)C>CC1C=CC=CC=1[P](C1C=CC=CC=1C)([Pd](Cl)(Cl)[P](C1=C(C)C=CC=C1)(C1C=CC=CC=1C)C1C=CC=CC=1C)C1C=CC=CC=1C.CN(C=O)C.O>[C:7]1([CH2:6][CH:2]([NH:1][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:3]([OH:5])=[O:4])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

8

Reactant 5

HCID 312ChlorideHCID 6140L-PhenylalanineHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 11575Iodobenzene

Product 1

HCID 134164113-Phenyl-2-(phenylamino)propanoic acidYield 56%

Reagents, catalysts & solvents 2

HCID 178424406HCID 178424406, compoundCatalystHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

To a solution of (S)-2-amino-3-phenylpropanoic acid (1.52 g, 9.12 mmol) in a DMF/H2O mixture (10/1, 16.5 mL) maintained under nitrogen flowstream, iodobenzene (1.00 mL, 9.12 mmol), dichlorobis(tri-o-tolylphosphine)palladium(II) (357 mg, 0.42 mmol) CuI (86.4 mg, 0.42 mmol), K2CO3 (1.21 g, 9.12 mmol), rimethylbenzylammonium chloride (286 mg, 1.51 mmol) and triethylamine (TEA) (2.50 mL, 18.0 mmol) are added and the mixture stirred for 24 hours at 100° C. under nitrogen flowstream (LC-MS monitoring: complete conversion). The reaction mixture is partitioned between EtOAc and water; 1N HCl is added until pH=1 and the organic layer is separated, washed with brine and dried over Na2SO4. The resulting crude is purified by flash chromatography (DCM/MeOH=99/1) and 1.21 g of I21 is obtained (56% yield).

Workup

  1. additionare added
  2. customThe reaction mixture is partitioned between EtOAc and water
  3. addition1N HCl is added until pH=1
  4. customthe organic layer is separated
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. customThe resulting crude is purified by flash chromatography (DCM/MeOH=99/1) and 1.21 g of I21
  8. customis obtained (56% yield)

Sources & evidence

ORD record
ord-09b285d5a4da49b981d1903a7bcfd70e
Source dataset
uspto-grants-2014_09
Patent number
US08835682B2

Reaction notes

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