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

HRID 705563Notes

Reaction equation

HRID 705563 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-e115f50148924e64b95056b44c44182e
Source dataset
uspto-grants-2015_11
Patent number
US09174970B2

Reaction notes

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