Potassium Carbonate → Methyl 6-(4-(2-(tert-butyldimethylsilyloxy)ethoxy)-2,6-difluorophenyl)-5-fluoropicolinate

HRID 879103Notes

Reaction equation

HRID 879103 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[C:4]([F:9])[C:3]=1[C:10]1[N:15]=[C:14]([C:16]([O:18][CH3:19])=[O:17])[CH:13]=[CH:12][C:11]=1[F:20].C(=O)([O-])[O-].[K+].[K+].Br[CH2:28][CH2:29][O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32]>CN(C=O)C.O>[Si:31]([O:30][CH2:29][CH2:28][O:8][C:6]1[CH:5]=[C:4]([F:9])[C:3]([C:10]2[N:15]=[C:14]([C:16]([O:18][CH3:19])=[O:17])[CH:13]=[CH:12][C:11]=2[F:20])=[C:2]([F:1])[CH:7]=1)([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilaneHCID 136350310Methyl 6-(2,6-difluoro-4-hydroxyphenyl)-5-fluoropicolinate

Product 1

HCID 66652485Methyl 6-(4-(2-(tert-butyldimethylsilyloxy)ethoxy)-2,6-difluorophenyl)-5-fluoropicolinateYield 74%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl 6-(2,6-difluoro-4-hydroxyphenyl)-5-fluoropicolinate (1.0 equiv.) and potassium carbonate (4.0 equiv.) in DMF (0.4 M) was added (2-bromoethoxy)(tert-butyl)dimethylsilane (2 equiv.). After stirring for 72 hours at rt the heterogeneous solution was diluted with water, extracted with EtOAc, dried over MgSO4, filtered, concentrated and purified by ISCO SiO2 chromatography to yield methyl 6-(4-(2-(tert-butyldimethylsilyloxy)ethoxy)-2,6-difluorophenyl)-5-fluoropicolinate in 74% yield. LC/MS=442.1 (M+H), Rt=1.22 min.

Workup

  1. extractionextracted with EtOAc
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custompurified by ISCO SiO2 chromatography

Sources & evidence

ORD record
ord-95e7fdbf260f4ae3a551e86a0411722d
Source dataset
uspto-grants-2015_03
Patent number
US08987457B2

Reaction notes

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