Bromine → Methyl 4-amino-5-bromo-3-chloro-6-(2,5-difluoro-4-(trimethylsilyl)phenyl)picolinate

HRID 516589Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[C:12]([F:14])[C:11]([Si:15]([CH3:18])([CH3:17])[CH3:16])=[CH:10][C:9]=2[F:19])[N:5]=[C:4]([C:20]([O:22][CH3:23])=[O:21])[C:3]=1[Cl:24].[Br:25]Br.[O-]S([O-])(=S)=O.[Na+].[Na+]>C(Cl)Cl>[NH2:1][C:2]1[C:7]([Br:25])=[C:6]([C:8]2[CH:13]=[C:12]([F:14])[C:11]([Si:15]([CH3:17])([CH3:18])[CH3:16])=[CH:10][C:9]=2[F:19])[N:5]=[C:4]([C:20]([O:22][CH3:23])=[O:21])[C:3]=1[Cl:24]

Participants

Conditions

Temperature: 20 °C

Procedure

To a solution of methyl 4-amino-3-chloro-6-(2,5-difluoro-4-(trimethylsilyl)phenyl)picolinate (0.210 g, 0.566 mmol) in CH2Cl2 (2.265 mL) at 20° C. was added bromine (0.117 mL, 2.265 mmol). The reaction mixture was stirred at 20° C. overnight. The mixture was then poured into a saturated aqueous solution of Na2S2O3 and extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography (SiO2, hexanes/EtOAc gradient) to provide the title compound as a white solid (0.125 g, 49.1%): mp 165-166° C.; 1H NMR (400 MHz, CDCl3) δ 7.10 (dd, J=8.9, 4.0 Hz, 1H), 7.03 (dd, J=7.6, 5.1 Hz, 1H), 5.43 (s, 2H), 3.96 (s, 3H), 0.33 (d, J=0.7 Hz, 9H); ESIMS m/z 450 ([M+H]+).

Workup

extractionextracted with EtOAc (3×)
dry with materialThe combined organic layers were dried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified by flash column chromatography (SiO2, hexanes/EtOAc gradient)

Sources & evidence

ORD record: ord-5ba70510350a4626856d2a7d93ca678c
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09113629B2

Reaction notes

Loading…