Diethyl Ether → [5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]-triethylsilanylamine

HRID 1500010Notes

Reaction equation

HRID 1500010 reaction equation
[F:1][C:2]1[C:3]([NH2:17])=[N:4][C:5]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)=[N:6][CH:7]=1.[H-].[Na+].[CH2:20]([Si:22](Cl)([CH2:25][CH3:26])[CH2:23][CH3:24])[CH3:21].CCOCC>C1COCC1>[F:1][C:2]1[C:3]([NH:17][Si:22]([CH2:25][CH3:26])([CH2:23][CH3:24])[CH2:20][CH3:21])=[N:4][C:5]([O:8][CH2:9][C:10]2[CH:11]=[CH:12][C:13]([F:16])=[CH:14][CH:15]=2)=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 13819ChlorotriethylsilaneHCID 24758Sodium hydrideHCID 578185745-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-amine

Product 1

HCID 57818999[5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]-triethylsilanylamineYield 33%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a magnetically stirred mixture of 5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-ylamine (0.25 g, 1.05 mmol) in dry THF (5 mL) at 0° C. was added NaH (0.042 g of 60 wt. % suspension in mineral oil, 1.05 mmol). When bubbling ceased, triethylsilyl chloride (0.158 g, 1.05 mmol) was added dropwise (neat) via syringe. After stirring overnight at ambient temperature, the reaction mixture was poured into ether and washed with a mixture of aqueous saturated sodium bicarbonate and brine solution. The organic layer was separated, dried over Na2SO4, filtered, and evaporated to give a white solid. This crude material was purified on silica by column chromatography (EtOAc/hexanes gradient) to give 0.121 g (33%) of [5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]-triethylsilanylamine as a clear yellow oil: 1H NMR (300 MHz, CDCl3) δ 7.89 (d, J=2.5 Hz, 1H), 7.39 (m, 2H), 7.03 (t, J=8.6 Hz, 2H), 5.27 (s, 2H), 4.53 (s, 1H), 0.99 (m, 9H), 0.83 (m, 6H); HPLC-MS (ESI) m/z 352 (M+H)+.

Workup

  1. customWhen bubbling
  2. washwashed with a mixture of aqueous saturated sodium bicarbonate and brine solution
  3. customThe organic layer was separated
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customto give a white solid
  8. customThis crude material was purified on silica by column chromatography (EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-ac88bb04486545c0b43ee127fd0fb133
Source dataset
uspto-grants-2015_12
Patent number
US09204653B2

Reaction notes

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