Potassium Carbonate → ethyl (alphaS)-alpha-[[(1,1-dimethylethoxy)carbonyl]amino]-4'-ethoxymethyl-2',6'-dimethoxy(1,1'-biphenyl)-4-propionate

HRID 1454111Notes

Reaction equation

HRID 1454111 reaction equation
[CH3:1][C:2]([CH3:22])([O:4][C:5]([NH:7][C@@H:8]([CH2:14][C:15]1[CH:20]=[CH:19][C:18](Br)=[CH:17][CH:16]=1)[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[O:6])[CH3:3].[CH2:23]([O:25][CH2:26][C:27]1[CH:32]=[C:31]([O:33][CH3:34])[C:30](B(O)O)=[C:29]([O:38][CH3:39])[CH:28]=1)[CH3:24].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.CN1CCCC1=O>[CH3:1][C:2]([CH3:22])([O:4][C:5]([NH:7][C@@H:8]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:30]2[C:29]([O:38][CH3:39])=[CH:28][C:27]([CH2:26][O:25][CH2:23][CH3:24])=[CH:32][C:31]=2[O:33][CH3:34])=[CH:17][CH:16]=1)[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[O:6])[CH3:3]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 10236170(4-(Ethoxymethyl)-2,6-dimethoxyphenyl)boronic acidHCID 69597080N-Boc-4-bromo-L-phenylalanine ethyl ester

Product 1

HCID 11329259ethyl (alphaS)-alpha-[[(1,1-dimethylethoxy)carbonyl]amino]-4'-ethoxymethyl-2',6'-dimethoxy(1,1'-biphenyl)-4-propionateYield 139.4%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

Under nitrogen atmosphere, a mixture of ethyl (αS)-α-[[(1,1-dimethylethoxy)carbonyl]amino]-4-bromobenzene propanoate (11.17 g), 4-ethoxymethyl-2,6-dimethoxyphenylboronic acid (10.80 g), palladium acetate (0.34 g), triphenylphosphine (1.57 g), anhydrous potassium carbonate (12.44 g), N-methylpyrrolidone (56 ml) and water (11 ml) was stirred for 50 minutes at 80° C. After completion of the reaction, the mixture was cooled to room temperature and extracted with ethyl acetate and water. The organic layer was washed with 10% aqueous citric acid solution and saturated aqueous NaCl solution, dried over magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure to yield ethyl (αS)-α-[[(1,1-dimethylethoxy)carbonyl]amino]-4′-ethoxymethyl-2′,6′-dimethoxy(1,1′-biphenyl)-4-propionate (20.4 g) as oil.

Workup

  1. customAfter completion of the reaction
  2. temperaturethe mixture was cooled to room temperature
  3. extractionextracted with ethyl acetate and water
  4. washThe organic layer was washed with 10% aqueous citric acid solution and saturated aqueous NaCl solution
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltrated
  7. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-9897b36671f44fc89a04441963d359a2
Source dataset
uspto-grants-2009_01
Patent number
US07476758B2

Reaction notes

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