Carbamic acid, N-methyl-, ethyl ester → [4-Cyclopropyl-2-(4-trifluoromethyl-phenyl)-pyrimidin-5-ylmethyl]-methyl-carbamic acid ethyl ester

HRID 1242488Notes

Reaction equation

HRID 1242488 reaction equation
Cl[CH2:2][C:3]1[C:4]([CH:19]2[CH2:21][CH2:20]2)=[N:5][C:6]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=2)=[N:7][CH:8]=1.[CH2:22]([O:24][C:25](=[O:28])[NH:26][CH3:27])[CH3:23].[H-].[Na+].Cl.O>CN(C=O)C>[CH2:22]([O:24][C:25](=[O:28])[N:26]([CH2:2][C:3]1[C:4]([CH:19]2[CH2:21][CH2:20]2)=[N:5][C:6]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=2)=[N:7][CH:8]=1)[CH3:27])[CH3:23]

Participants

6

Reactant 4

HCID 7752Carbamic acid, N-methyl-, ethyl esterHCID 24758Sodium hydrideHCID 21885828Hydrate;hydrochlorideHCID 219359605-Chloromethyl-4-cyclopropyl-2-(4-trifluoromethyl-phenyl)-pyrimidine

Product 1

HCID 69525511[4-Cyclopropyl-2-(4-trifluoromethyl-phenyl)-pyrimidin-5-ylmethyl]-methyl-carbamic acid ethyl esterYield 71.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

1.00 g (3.2 mmol) of 5-chloromethyl-4-cyclopropyl-2-(4-trifluoromethyl-phenyl)-pyrimidine (example 27F]) was dissolved in 20 ml of DMF. Then, the reaction mixture was cooled down to 0° C. 0.36 ml=0.366 g (3.52 mmol) of methyl-carbamic acid ethyl ester was added to the stirred solution, followed by 0.14 g (3.2 mmol) of sodium hydride (55%). After 18 hours, the reaction mixture was poured into crashed ice, the pH was adjusted to <3 with HCl/H2O and it was then extracted twice with Et2O. The combined organic phases were washed with water, dried over anhydrous magnesium sulfate and evaporated. The crude product was purified by flash chromatography (SiO2, gradient of EtOAc, n-heptane) to give 0.87 g of the title compound as light yellow solid.

Workup

  1. additionthe reaction mixture was poured
  2. extractionwas then extracted twice with Et2O
  3. washThe combined organic phases were washed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customevaporated
  6. customThe crude product was purified by flash chromatography (SiO2, gradient of EtOAc, n-heptane)

Sources & evidence

ORD record
ord-e916fff632cf422bb51e1a640781cd07
Source dataset
uspto-grants-2006_10
Patent number
US07115611B2

Reaction notes

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