Methyl 6-bromo-5-fluoropyridine-2-carboxylate → Methyl 6-(2,6-difluoro-4-(2-hydroxypropan-2-yl)phenyl)-5-fluoropicolinate

HRID 879107Notes

Reaction equation

HRID 879107 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[CH:4][C:3]=1[F:12].[F:13][C:14]1[CH:15]=[C:16]([C:30]([O:33][Si](C(C)C)(C(C)C)C(C)C)([CH3:32])[CH3:31])[CH:17]=[C:18]([F:29])[C:19]=1B1OC(C)(C)C(C)(C)O1>>[F:13][C:14]1[CH:15]=[C:16]([C:30]([OH:33])([CH3:32])[CH3:31])[CH:17]=[C:18]([F:29])[C:19]=1[C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[CH:4][C:3]=1[F:12]

Participants

3

Reactant 2

HCID 46311204Methyl 6-bromo-5-fluoropyridine-2-carboxylateHCID 66652369(2-(3,5-Difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-yloxy)triisopropylsilane

Product 1

HCID 66655918Methyl 6-(2,6-difluoro-4-(2-hydroxypropan-2-yl)phenyl)-5-fluoropicolinateYield 90%

Procedure

Method 1 was followed using methyl 6-bromo-5-fluoropicolinate (1.0 equiv.) and (2-(3,5-difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-yloxy)triisopropylsilane (1.6 equiv.) at 100° C. for 30 min in the microwave to give methyl 6-(2,6-difluoro-4-(2-hydroxypropan-2-yl)phenyl)-5-fluoropicolinate in 90% yield. LC/MS=325.9 (MH+), Rt=0.81 min. 1H NMR (400 MHz, <cdcl3>) δ ppm 1.59 (s, 6H), 4.00 (s, 3H), 7.15 (d, J=9.00 Hz, 2H), 7.62-7.68 (m, 1H), 8.23-8.29 (m, 1H).

Workup

  1. customat 100° C.
  2. customfor 30 min

Sources & evidence

ORD record
ord-e440cb66335941f38fa5d9ca3b27f391
Source dataset
uspto-grants-2015_03
Patent number
US08987457B2

Reaction notes

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