Dimethyl Sulfate → Methyl (2E)-2-(2-((6-chloropyrimidin-4-yl)oxy)phenyl)-3-methoxyprop-2-enoate

HRID 2060647Notes

Reaction equation

HRID 2060647 reaction equation
[CH:1]([O:6]C)([O:4][CH3:5])OC.[Cl:8][C:9]1[N:14]=[CH:13][N:12]=[C:11]([O:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[CH2:22][C:23]([O:25][CH3:26])=O)[CH:10]=1.[OH-].[Na+].S(OC)(OC)(=O)=O>C1(C)C=CC=CC=1.[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.[Ti](Cl)(Cl)(Cl)Cl.C(N(CC)CC)C.ClCCl>[Cl:8][C:9]1[N:14]=[CH:13][N:12]=[C:11]([O:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2/[C:22](=[CH:23]\[O:25][CH3:26])/[C:1]([O:4][CH3:5])=[O:6])[CH:10]=1

Participants

10

Reactant 4

HCID 6497Dimethyl SulfateHCID 9005Trimethyl orthoformateHCID 14798Sodium HydroxideHCID 22020169Methyl {2-[(6-chloropyrimidin-4-yl)oxy]phenyl}acetate

Product 1

HCID 11782200Methyl (2E)-2-(2-((6-chloropyrimidin-4-yl)oxy)phenyl)-3-methoxyprop-2-enoateYield 91.3%

Reagents, catalysts & solvents 5

HCID 24193Titanium TetrachlorideCatalystHCID 66133Benzyl triethylammonium chlorideCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

Under the dried nitrogen atmosphere, to a reaction flask were added 150 mL of dichloromethane and 11.4 g of titanium tetrachloride, and then 6.4 g of trimethyl orthoformate was further added under violent stirring. After being stirred at room temperature for 1 hr, the mixture was cooled to −5° C., followed by adding thereto 13.9 g of methyl 2-(2-(6-chloropyrimidin-4-oxy)phenyl)acetate. The resultant was stirred for 30 min, and then 12.1 g of triethylamine was added and the resultant was stirred for 1 hr. The resulting reaction mixture was washed with 40 mL of 10% hydrochloric acid, dried with anhydrous magnesium sulfate and evaporated under vacuum to obtain a brown viscous substance. The brown viscous substance was dissolved in 100 mL of hot toluene, cooled to room temperature and then treated with 0.9 g of benzyltriethylammonium chloride, 15 g of 20% sodium hydroxide aqueous solution and 12.6 g of dimethyl sulfate. After that, the mixture was stirred at room temperature for 5 hrs, followed by being heated to 50° C., and the reaction went on under stirring for another 1 hr. The resulting mixture was washed with 50 mL of water, evaporated under reduced pressure and purified with flash column chromatography to obtain 14.6 g pale yellow solid. The yield was 91%.

Workup

  1. temperaturethe mixture was cooled to −5° C.
  2. additionby adding
  3. stirringThe resultant was stirred for 30 min
  4. stirringthe resultant was stirred for 1 hr
  5. customThe resulting reaction mixture
  6. washwas washed with 40 mL of 10% hydrochloric acid
  7. dry with materialdried with anhydrous magnesium sulfate
  8. customevaporated under vacuum
  9. customto obtain a brown viscous substance
  10. temperaturecooled to room temperature
  11. stirringAfter that, the mixture was stirred at room temperature for 5 hrs
  12. temperatureby being heated to 50° C.
  13. stirringunder stirring for another 1 hr
  14. washThe resulting mixture was washed with 50 mL of water
  15. customevaporated under reduced pressure
  16. custompurified with flash column chromatography

Sources & evidence

ORD record
ord-3c703c249bbc42cbb2b8c1f94a7c5605
Source dataset
uspto-grants-2012_10
Patent number
US08278445B2

Reaction notes

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