Cesium fluoride → methyl 2(S)-ethoxy-3-{4-[6-(3-heptyl-1-methylureido)pyrid-2-yl]phenyl}propanoate

HRID 2426317

Reaction equation

HRID 2426317 reaction equation
Br[C:2]1[N:7]=[C:6]([N:8]([CH3:19])[C:9]([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])=[O:10])[CH:5]=[CH:4][CH:3]=1.[CH2:20]([O:22][C@@H:23]([CH2:28][C:29]1[CH:34]=[CH:33][C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][CH:30]=1)[C:24]([O:26][CH3:27])=[O:25])[CH3:21].[F-].[Cs+]>COC(O)C(O)OC>[CH2:20]([O:22][C@@H:23]([CH2:28][C:29]1[CH:34]=[CH:33][C:32]([C:2]2[CH:3]=[CH:4][CH:5]=[C:6]([N:8]([CH3:19])[C:9]([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])=[O:10])[N:7]=2)=[CH:31][CH:30]=1)[C:24]([O:26][CH3:27])=[O:25])[CH3:21]

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 67147872methyl 2(S)-ethoxy-3-[4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenyl]propanoateHCID 860188681-(6-Bromopyrid-2-yl)-1-methyl-3-heptylurea

Product 1

HCID 67148298methyl 2(S)-ethoxy-3-{4-[6-(3-heptyl-1-methylureido)pyrid-2-yl]phenyl}propanoateYield 45.3%

Reagents, catalysts & solvents 1

HCID 21263609Dimethoxy ethylene glycolSolvent

Conditions

Temperature
80 °C

Procedure

3.2 g (9.7 mmol) of 1-(6-bromopyrid-2-yl)-3-heptyl-1-methylurea, 4.2 g (12.6 mmol) of methyl 2(S)-ethoxy-3-[4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenyl]propanoate (prepared as in Example 7e) and 4.4 g (29.1 mmol) of caesium fluoride are placed in 200 ml of dimethoxyethylene glycol. The reaction medium is degassed, 0.23 g (0.3 mmol) of dichlorodiphenylphosphinoferrocenepalladium is then added and the reaction medium is stirred at 80° C. for 18 hours. After addition of water, the reaction medium is extracted with ethyl acetate. The organic phase is washed with water, with saturated sodium chloride solution, dried over magnesium sulfate, filtered and evaporated. The residue obtained is purified by thin-layer chromatography on silica eluted with an 80/20 heptane/ethyl acetate mixture. 2 g (45%) of methyl 2(S)-ethoxy-3-{4-[6-(3-heptyl-1-methylureido)pyrid-2-yl]phenyl}propanoate are obtained.

Workup

  1. customThe reaction medium is degassed
  2. addition0.23 g (0.3 mmol) of dichlorodiphenylphosphinoferrocenepalladium is then added
  3. additionAfter addition of water
  4. extractionthe reaction medium is extracted with ethyl acetate
  5. washThe organic phase is washed with water, with saturated sodium chloride solution
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue obtained
  10. customis purified by thin-layer chromatography on silica
  11. washeluted with an 80/20 heptane/ethyl acetate mixture

Sources & evidence

ORD record
ord-546962a0e8a848458b11c0e6cfcb7eb3
Source dataset
uspto-grants-2011_06
Patent number
US07968560B2

Linked notes

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