Benzyl Alcohol → 3-(2,6-Bis-benzyloxy-5-isopropyl-pyrimidin-4-yloxy)-5-methyl-benzonitrile

HRID 2194801Notes

Reaction equation

[H-].[Na+].[CH2:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl[C:12]1[N:17]=[C:16]([O:18][C:19]2[CH:20]=[C:21]([CH:24]=[C:25]([CH3:27])[CH:26]=2)[C:22]#[N:23])[C:15]([CH:28]([CH3:30])[CH3:29])=[C:14](Cl)[N:13]=1.C([O:35][CH2:36][CH3:37])(=O)C>C1COCC1>[CH2:3]([O:10][C:12]1[N:17]=[C:16]([O:18][C:19]2[CH:20]=[C:21]([CH:24]=[C:25]([CH3:27])[CH:26]=2)[C:22]#[N:23])[C:15]([CH:28]([CH3:30])[CH3:29])=[C:14]([O:35][CH2:36][C:37]2[CH:8]=[CH:9][CH:4]=[CH:5][CH:6]=2)[N:13]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

Conditions

Temperature: 0 °C

Procedure

At 0° C., NaH (60%, 118 mg, 2.88 mmol, 2.2 eq.) was added to benzyl alcohol (298 μL, 2.88 mmol) in 5 mL of THF solution. The reaction mixture was stirred at 0° C. for 5 minutes. 3-(2,6-Dichloro-5-isopropyl-pyrimidin-4-yloxy)-5-methyl-benzonitrile (422 mg, 1.31 mmol) was added. The reaction mixture was stirred at 0° C. for 15 minutes, then warmed to room temperature for 90 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 (372 mg, 65% pure by HPLC, 40%). LC-MS shows 466.1 (M+1).

Workup

stirringThe reaction mixture was stirred at 0° C. for 15 minutes
temperaturewarmed to room temperature for 90 minutes
washwas then washed with brine
concentrationThe organic layer was concentrated
custompurified (silica gel, 0-50% EtOAc/hexane)
customto give a white solid (372 mg, 65% pure by HPLC, 40%)

Sources & evidence

ORD record: ord-e5482a055001437fb7f4b07c1f402350
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08334295B2

Reaction notes

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