N-bromobutanimide → Propan-2-yl 4-amino-3-bromo-5-fluoro-6-(4-chloro-2-fluoro-3-methoxyphenyl)picolinate

HRID 1424657Notes

Reaction equation

HRID 1424657 reaction equation
[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[C:11]([O:16][CH3:17])[C:10]=2[F:18])[N:5]=[C:4]([C:19]([O:21][CH:22]([CH3:24])[CH3:23])=[O:20])[CH:3]=1.[Br:25]N1C(=O)CCC1=O>ClCCl>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[C:11]([O:16][CH3:17])[C:10]=2[F:18])[N:5]=[C:4]([C:19]([O:21][CH:22]([CH3:24])[CH3:23])=[O:20])[C:3]=1[Br:25]

Participants

4

Reactant 2

HCID 67184N-bromobutanimideHCID 70497595Isopropyl 4-(amino)-6-(4-chloro-2-fluoro-3-methoxyphenyl)-5-fluoro-picolinate

Product 1

HCID 70496076Propan-2-yl 4-amino-3-bromo-5-fluoro-6-(4-chloro-2-fluoro-3-methoxyphenyl)picolinateYield 83%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Propan-2-yl 4-amino-5-fluoro-6-(4-chloro-2-fluoro-3-methoxyphenyl)picolinate (500 mg, 1.402 mmol) was dissolved in dichloromethane (3.2 mL). N-Bromo-succinimide (299 mg, 1.682 mmol) was added, and the solution was stirred at ambient temperature for 20 h. The reaction mixture was then concentrated to dryness. The residue was purified by chromatography (40 g silica gel column; 0-70% EtOAc-hexanes) to give a tan solid (504 mg, 83%): 1H NMR (400 MHz, DMSO-d6) δ 7.47 (dd, J=8.5, 1.6 Hz, 1H), 7.29 (dd, J=8.5, 7.1 Hz, 1H), 7.01 (s, 2H), 5.22-5.10 (m, 1H), 3.93 (d, J=0.9 Hz, 3H), 1.32 (d, J=6.3 Hz, 6H); EIMS m/z 350.

Workup

  1. concentrationThe reaction mixture was then concentrated to dryness
  2. customThe residue was purified by chromatography (40 g silica gel column; 0-70% EtOAc-hexanes)

Sources & evidence

ORD record
ord-3989e11c3e9a4584b9aaa7b24bd2fb41
Source dataset
uspto-grants-2015_01
Patent number
US08927731B2

Reaction notes

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