2-Methyl-2-butene → (2-(4-Methylthiazol-2-ylamino)pyridin-4-yloxy)phenol

HRID 910930Notes

Reaction equation

C[O:2][C:3]1[CH:22]=[CH:21][CH:20]=[CH:19][C:4]=1[O:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]([NH:12][C:13]2[S:14][CH:15]=[C:16]([CH3:18])[N:17]=2)[CH:7]=1.BrB(Br)Br.CC(=CC)C.C([O-])(O)=O.[Na+]>O.ClCCl>[CH3:18][C:16]1[N:17]=[C:13]([NH:12][C:8]2[CH:7]=[C:6]([O:5][C:4]3[CH:19]=[CH:20][CH:21]=[CH:22][C:3]=3[OH:2])[CH:11]=[CH:10][N:9]=2)[S:14][CH:15]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A 50 mL round bottom flask was charged with 4-(2-methoxyphenoxy)-N-(4-methylthiazol-2-yl)pyridin-2-amine (6.38 mL, 0.638 mmol) and dichloromethane (6 mL). The solution was cooled to 0° C., and tribromoborane (0.181 mL, 1.91 mmol) and 1 mL of 2-methyl-2-butene were added. The reaction mixture was stirred at 0° C. for 1 hour. Water and saturated solution of NaHCO3 were added, and the reaction mixture was extracted with EtOAc. The organic layer was dried over magnesium sulfate, filtered and concentrated. The residue was purified on a prepacked silica gel column, eluting with 20-35% EtOAc in hexanes to give 2-(2-(4-methylthiazol-2-ylamino)pyridin-4-yloxy)phenol (0.130 g, 67.4% yield) as light yellow solid. 1H NMR (DMSO) δ 10.90 (bs, 1H), 9.70 (bs, 1H), 8.10 (d, 1H), 7.11 (m, 2H), 7.01 (dd, 1H), 6.87 (dt, 1H), 6.49 (d, 1H), 6.43 (m, 2H), 2.19 (d, 3H); Mass spectrum (esi) m/z=300 (100) (M+H).

Workup

extractionthe reaction mixture was extracted with EtOAc
dry with materialThe organic layer was dried over magnesium sulfate
filtrationfiltered
concentrationconcentrated
customThe residue was purified on a prepacked silica gel column
washeluting with 20-35% EtOAc in hexanes

Sources & evidence

ORD record: ord-b32590129213405898839ea1b47c0fcf
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08022222B2

Reaction notes

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