Nitrogen → HCID 59819879, compound

HRID 383608Notes

Reaction equation

HRID 383608 reaction equation
N#N.C[O:4][C:5](=[O:29])[C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13](=[O:28])[CH2:14][CH2:15][C:16]2[CH:21]=[C:20]([O:22]C)[C:19]([O:24]C)=[C:18]([O:26]C)[CH:17]=2)=[CH:8][CH:7]=1.B(Br)(Br)Br.[Cl-].[Na+].O.CCOC(C)=O>C(Cl)Cl.CO>[OH:22][C:20]1[CH:21]=[C:16]([CH2:15][CH2:14][C:13]([NH:12][C:9]2[CH:10]=[CH:11][C:6]([C:5]([OH:29])=[O:4])=[CH:7][CH:8]=2)=[O:28])[CH:17]=[C:18]([OH:26])[C:19]=1[OH:24]

Participants

7

Reactant 4

HCID 947NitrogenHCID 25134Boron tribromideHCID 40627700HCID 40627700, compoundHCID 131718255Brine ethyl acetate

Product 1

HCID 59819879HCID 59819879, compoundYield 44.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

(The following reaction is done in an anhydrous N2 atmosphere.) Dissolve 4-[3-(3,4,5-Trimethoxy-phenyl)-propionylamino]-benzoic acid methyl ester (78) (45 mg, 0.12 mmol) in anhydrous DCM (1.2 mL), cool the solution to −78° C. and add dropwise BBr3 (90 μL, 0.96 mmol). Stir the reaction mixture for 30 min at −78° C. and after slowly warming up for additional 3 h at rt. Add dropwise ice-water/THF (1+1) followed by MeOH and remove solvent. Purify the crude product by preparative RP HPLC (gradient, water/CH3CN 95:5 to 5:95) to obtain 4-[3-(3,4,5-Trihydroxy-phenyl)-propionylamino]-benzoic acid (79) (17 mg, 44%) as a white solid. 1H NMR (400 MHz, CD3OD): 2.65 (t, 2H, J=7.5 Hz); 2.83 (t, 2H, J=7.5 Hz); 6.29 (s, 2H); 7.68 (d, 2H, J=8.3 Hz); 7.99 (d, 2H, J=8.6 Hz).

Workup

  1. custom(The following reaction
  2. temperatureafter slowly warming up for additional 3 h at rt
  3. customremove solvent
  4. customPurify the crude product by preparative RP HPLC (gradient, water/CH3CN 95:5 to 5:95)

Sources & evidence

ORD record
ord-5870111a966843dd9c0c880562169861
Source dataset
uspto-grants-2013_02
Patent number
US08367677B2

Reaction notes

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