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

HRID 1499591Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([C:18]([OH:21])([CH3:20])[CH3:19])[CH:5]=[C:6]([F:17])[C:7]=1B1OC(C)(C)C(C)(C)O1.Br[C:23]1[N:28]=[C:27]([C:29]([O:31][CH3:32])=[O:30])[CH:26]=[CH:25][C:24]=1[F:33].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:17][C:6]1[CH:5]=[C:4]([C:18]([OH:21])([CH3:19])[CH3:20])[CH:3]=[C:2]([F:1])[C:7]=1[C:23]1[N:28]=[C:27]([C:29]([O:31][CH3:32])=[O:30])[CH:26]=[CH:25][C:24]=1[F:33]

Participants

Conditions

Temperature: 120 °C

Procedure

To a nitrogen purged mixture of 2-[3,5-difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propan-2-ol (1.53 g, 5.13 mmol), methyl 6-bromo-5-fluoropyridine-2-carboxylate (1.20 g, 5.13 mmol) and DIPEA (2.7 mL, 15 mmol) in 1,4-dioxane (20 mL) and water (1.2 mL), bis(tri-tert-butylphosphine)palladium (262 mg, 0.513 mmol) was added. The reaction mixture was heated at 120° C. for 40 min., then cooled and filtered through a pad of diatomaceous earth. The filtrate was concentrated under reduced pressure. The crude residue was purified by silica gel column chromatography (0-50% EtOAc in hexanes) to give methyl 6-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-5-fluoropyridine-2-carboxylate as a white powder, which was used without further purification.

Workup

customTo a nitrogen purged
additionwas added
temperaturecooled
filtrationfiltered through a pad of diatomaceous earth
concentrationThe filtrate was concentrated under reduced pressure
customThe crude residue was purified by silica gel column chromatography (0-50% EtOAc in hexanes)

Sources & evidence

ORD record: ord-a4d2cd6192e846ebb1974b468c6fcc8f
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09200004B2

Reaction notes

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