Potassium Carbonate → HCID 18394280, compound

HRID 1600567Notes

Reaction equation

HRID 1600567 reaction equation
[S:1]1[CH:5]=[CH:4][C:3](B(O)O)=[CH:2]1.C(=O)([O-])[O-].[K+].[K+].[CH3:15][O:16][C:17](=[O:42])[C@@H:18]([CH2:27][C:28]1[CH:33]=[CH:32][C:31](OS(C(F)(F)F)(=O)=O)=[CH:30][CH:29]=1)[NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21]>C1(C)C=CC=CC=1>[CH3:15][O:16][C:17](=[O:42])[C@@H:18]([CH2:27][C:28]1[CH:29]=[CH:30][C:31]([C:3]2[CH:4]=[CH:5][S:1][CH:2]=2)=[CH:32][CH:33]=1)[NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:24])[CH3:25])=[O:21]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 581760Thiophene-3-boronic acidHCID 53983472HCID 53983472, compound

Product 1

HCID 18394280HCID 18394280, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
80 °C

Procedure

To a solution of N-t-butoxycarbonyl-D-tyrosine methyl ester (2.5 g, 9.48 mmol) in 10 mL of methylene chloride and pyridine (1.9 mL, 23.7 mmol) at -15° C. is added triflic anhydride (1.9 mL, 11.4 mmol). The reaction is stirred 30 minutes. The mixture is washed with water, 0.5 N NaOH, 15% aqueous citric acid, brine dried over MgSO4, filtered and concentrated giving N-t-butoxycarbonyl-4-trifluoromethanesulfonyloxy-D-phenyl alanine methyl ester. A solution of 3-thiopheneboronic acid (1.4 g, 10.9 mmol), potassium carbonate (1.13 g, 8.2 mmol) in 25 mL of toluene is heated to 80° C. and the catalyst tetrakis (triphenyl phosphine)-Pd (0.19 g, 0.16 mmol) is added. N-t-Butoxycarbonyl-4-trifluoro methanesulfonyloxy-D-phenylalanine methyl ester (2.34 g, 5.47 mmol) in 25 mL of toluene is added dropwise and stirred at 80° C. for 3 hours. The mixture is filtered through Celite and washed with ethyl acetate. The organic layer is washed with 0.5 N NaOH (2×), 15% citric acid, water, brine, dried over MgSO4, filtered and concentrated. Chromatography on silica gel with ethyl acetate/toluene (1:5) gives N-t-butoxy carbonyl-4-(3-thienyl)-D-phenylalanine methyl ester. Treatment of the above with dilute HCl in 1,4-dioxane at room temperature overnight yields 4-(3-thienyl)-D-phenylalanine methyl ester hydrochloride.

Workup

  1. filtrationThe mixture is filtered through Celite
  2. washwashed with ethyl acetate
  3. washThe organic layer is washed with 0.5 N NaOH (2×), 15% citric acid, water, brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-8f46f44da14140a3afc5d2bb773bd342
Source dataset
uspto-grants-1999_11
Patent number
US05977075

Reaction notes

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