Toluene → (S)-Methyl 3-([1,1'-biphenyl]-4-yl)-2-((tert-butoxycarbonyl)amino)propanoate

HRID 466229Notes

Reaction equation

HRID 466229 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17](OS(C(F)(F)F)(=O)=O)=[CH:16][CH:15]=1)[C:10]([O-:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:28]1(B(O)O)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.[C:37](=O)([O-])[O-].[K+].[K+].C1(C)C=CC=CC=1>C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:16][CH:15]=1)[C:10]([O:12][CH3:37])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 86630639(S)-2-(t-butoxycarbonylamino)-3-[4-(trifluoromethylsulfonyloxy)-phenyl]-propionate

Product 1

HCID 10286882(S)-Methyl 3-([1,1'-biphenyl]-4-yl)-2-((tert-butoxycarbonyl)amino)propanoate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Procedure

Nitrogen is passed through a suspension of (S)-2-(t-butoxycarbonylamino)-3-[4-(trifluoromethylsulfonyloxy)-phenyl]-propionate (1.75 mmol), phenylboronic acid (3.5 mmol), anhydrous potassium carbonate (2.63 mmol) and toluene (17 mL) for 15 minutes. Tetrakis(triphenylphosphine)palladium(0) is added, and the mixture is heated at 85°-90° for 3 hours. The reaction mixture is cooled to 25°, diluted with ethyl acetate (17 mL) and washed sequentially with saturated sodium bicarbonate (1×20 mL), water (1×20 mL), 10% citric acid (1×20 mL), water (1×20 mL) and saturated sodium chloride solution (1×20 mL). The organic phase is concentrated, and the residue is purified by column chromatography (silica gel, hexane/ethyl acetate 2:1) to yield methyl (S)-2-(t-butoxycarbonylamino)-3-(4-biphenylyl)-propionate which can also be called N-(S)-t-butoxycarbonyl-(4-biphenyl)-alanine methyl ester, m.p. 83°-85°; [α]20D +54.81° (c=1, CHCl3).

Workup

  1. temperaturethe mixture is heated at 85°-90° for 3 hours
  2. temperatureThe reaction mixture is cooled to 25°
  3. washwashed sequentially with saturated sodium bicarbonate (1×20 mL), water (1×20 mL), 10% citric acid (1×20 mL), water (1×20 mL) and saturated sodium chloride solution (1×20 mL)
  4. concentrationThe organic phase is concentrated
  5. customthe residue is purified by column chromatography (silica gel, hexane/ethyl acetate 2:1)

Sources & evidence

ORD record
ord-46b35e19582f473bbe55bafbbd1f90ea
Source dataset
uspto-grants-1992_10
Patent number
US05155100

Reaction notes

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