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

HRID 2261828Notes

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].N#N.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>[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

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 evacuated and re-filled with N2 3 times. To this solution, Pd2(dba)3 (0.010 g), tricyclohexyl phosphine (PCy3, 10 mg), and aqueous K3PO4 (1.5 mL, 1.30 M) are added. The resulting mixture is heated at 50° C. for 2 hours under N2. The reaction mixture is cooled to room temperature and filtered through a pad of celite. The filtrate is concentrated, and 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

temperatureThe reaction mixture is cooled to room temperature
filtrationfiltered through a pad of celite
concentrationThe filtrate is concentrated
customthe residue is purified via silica gel chromatography
washeluting with 25% ethyl acetate in hexanes

Sources & evidence

ORD record: ord-8306de1719b6414892f35a2521d88398
Source dataset: uspto-grants-2010_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07846960B2

Reaction notes

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