Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate → 6-(4-Hydroxy-2-methyl-phenyl)-benzo[d]isoxazole-3-carboxylic acid ethyl ester

HRID 250258Notes

Reaction equation

HRID 250258 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([OH:17])[CH:5]=[CH:6][C:7]=1B1OC(C)(C)C(C)(C)O1.[CH2:18]([O:20][C:21]([C:23]1[C:27]2[CH:28]=[CH:29][C:30](Br)=[CH:31][C:26]=2[O:25][N:24]=1)=[O:22])[CH3:19]>O1CCOCC1>[CH2:18]([O:20][C:21]([C:23]1[C:27]2[CH:28]=[CH:29][C:30]([C:7]3[CH:6]=[CH:5][C:4]([OH:17])=[CH:3][C:2]=3[CH3:1])=[CH:31][C:26]=2[O:25][N:24]=1)=[O:22])[CH3:19]

Participants

4

Reactant 2

HCID 53401270Ethyl 6-bromobenzo[d]isoxazole-3-carboxylateHCID 574432723-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol

Product 1

HCID 1363439726-(4-Hydroxy-2-methyl-phenyl)-benzo[d]isoxazole-3-carboxylic acid ethyl esterYield 93%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenol (0.624 g, 2.67 mmol) and 6-bromo-benzo[d]isoxazole-3-carboxylic acid ethyl ester (0.360 g, 1.33 mmol) in 1,4-dioxane (20 mL) is added to a flask. The flask is evacuated and re-filled with N2 3 times. To this solution, Pd2(dba)3 (0.010 g), tricyclohexyl phosphine (10 mg), and aqueous K3PO4 (1.5 mL, 1.30 M) are added. The resulting mixture is heated to 50° C. for 2 hours under N2. The reaction mixture is cooled to room temperature and filtered through a pad of diatomaceous earth. The filtrate is concentrated under reduced pressure. The residue is purified via silica gel chromatography eluting with 25% ethyl acetate in hexanes to give the title compound (0.366 g, 93%). ES/MS m/e 298.0 (M+1); 296.0 (M−1).

Workup

  1. customThe flask is evacuated
  2. additionre-filled with N2 3 times
  3. additionTo this solution, Pd2(dba)3 (0.010 g), tricyclohexyl phosphine (10 mg), and aqueous K3PO4 (1.5 mL, 1.30 M) are added
  4. temperatureThe reaction mixture is cooled to room temperature
  5. filtrationfiltered through a pad of diatomaceous earth
  6. concentrationThe filtrate is concentrated under reduced pressure
  7. customThe residue is purified via silica gel chromatography
  8. washeluting with 25% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-ab1bccaed9ff409dba5d89263ba75c26
Source dataset
uspto-grants-2011_01
Patent number
US07863302B2

Reaction notes

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