Ethyl Acetate → 3-(2,6-Dichloro-5-isopropyl-pyrimidin-4-yloxy)-5-methyl-benzonitrile

HRID 2194800Notes

Reaction equation

HRID 2194800 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:5]=[C:6]([CH:9]=[C:10]([CH3:12])[CH:11]=1)[C:7]#[N:8].[Cl:13][C:14]1[N:19]=[C:18](Cl)[C:17]([CH:21]([CH3:23])[CH3:22])=[C:16]([Cl:24])[N:15]=1.C(OCC)(=O)C>CN(C=O)C>[Cl:13][C:14]1[N:19]=[C:18]([O:3][C:4]2[CH:5]=[C:6]([CH:9]=[C:10]([CH3:12])[CH:11]=2)[C:7]#[N:8])[C:17]([CH:21]([CH3:22])[CH3:23])=[C:16]([Cl:24])[N:15]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 2490092,4,6-Trichloro-5-isopropylpyrimidineHCID 219498233-Hydroxy-5-methylbenzonitrile

Product 1

HCID 596868583-(2,6-Dichloro-5-isopropyl-pyrimidin-4-yloxy)-5-methyl-benzonitrileYield 88%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

At 0° C., NaH (60%, 125 mg, 3.06 mmol, 1.0 eq.) was added to 3-hydroxy-5-methyl-benzonitrile (408 mg, 3.06 mmol) in 10 mL of DMF solution. The reaction mixture was stirred at 0° C. for 5 minutes. 2,4,6-Trichloro-5-isopropyl-pyrimidine (691 mg, 3.06 mmol) was then added. The reaction mixture was stirred at 0° C. for 30 minutes. Ethyl acetate was added to the reaction mixture, which was then washed with brine. The organic layer was concentrated and purified (silica gel, 0-50% EtOAc/hexane) to give a white solid (868 mg, 88%). LC-MS shows 322.1 (M+1). 1H NMR (300 MHz, CDCl3): δ 7.41 (s, 1H), 7.26 (s, 1H), 7.19 (s, 1H), 3.60 (m, 1H), 2.42 (s, 3H), 1.42 (d, 6H).

Workup

  1. stirringThe reaction mixture was stirred at 0° C. for 30 minutes
  2. washwas then washed with brine
  3. concentrationThe organic layer was concentrated
  4. custompurified (silica gel, 0-50% EtOAc/hexane)

Sources & evidence

ORD record
ord-4ebba6757afd4cc2b2c00789f02cc1d9
Source dataset
uspto-grants-2012_12
Patent number
US08334295B2

Reaction notes

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