Diisopropylethylamine → Methyl 6-(2,6-difluoro-4-(methoxymethyl)phenyl)-5-fluoropicolinate

HRID 1499582Notes

Reaction equation

[F:1][C:2]1[CH:7]=[C:6]([CH2:8][O:9][CH3:10])[CH:5]=[C:4]([F:11])[C:3]=1B1OC(C)(C)C(C)(C)O1.Br[C:22]1[N:27]=[C:26]([C:28]([O:30][CH3:31])=[O:29])[CH:25]=[CH:24][C:23]=1[F:32].CCN(C(C)C)C(C)C>O1CCOCC1.O.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[F:11][C:4]1[CH:5]=[C:6]([CH2:8][O:9][CH3:10])[CH:7]=[C:2]([F:1])[C:3]=1[C:22]1[N:27]=[C:26]([C:28]([O:30][CH3:31])=[O:29])[CH:25]=[CH:24][C:23]=1[F:32]

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 2-[2,6-difluoro-4-(methoxymethyl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.364 g, 1.28 mmol), methyl 6-bromo-5-fluoropyridine-2-carboxylate (0.300 g, 1.28 mmol) and DIPEA (0.67 mL, 3.8 mmol) in 1,4-dioxane (6 mL) and water (0.30 mL) was purged with nitrogen. Bis(tri-tert-butylphosphine)palladium (65.5 mg, 0.128 mmol) was added to the mixture. The resulting reaction mixture was then heated at 120° C. for 40 min. The mixture was filtered through a pad of diatomaceous earth and the filtrate was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluting with 0-50% EtOAc in hexanes) to give methyl 6-[2,6-difluoro-4-(methoxymethyl)phenyl]-5-fluoropyridine-2-carboxylate as a white powder.

Workup

customwas purged with nitrogen
customThe resulting reaction mixture
filtrationThe mixture was filtered through a pad of diatomaceous earth
concentrationthe filtrate was concentrated under reduced pressure
customThe crude product was purified by silica gel column chromatography (eluting with 0-50% EtOAc in hexanes)

Sources & evidence

ORD record: ord-4f8a6614276f4955b841679e7108227b
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09200004B2

Reaction notes

Loading…