Sodium hydride → 2-(2-(2-Methoxy-4-nitrophenoxy)ethyl)tetrahydrofuran

HRID 2420719Notes

Reaction equation

HRID 2420719 reaction equation
[O:1]1[CH2:5][CH2:4][CH2:3][CH:2]1[CH2:6][CH2:7][OH:8].[H-].[Na+].Cl[C:12]1[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][C:13]=1[O:21][CH3:22]>CS(C)=O>[CH3:22][O:21][C:13]1[CH:14]=[C:15]([N+:18]([O-:20])=[O:19])[CH:16]=[CH:17][C:12]=1[O:8][CH2:7][CH2:6][CH:2]1[CH2:3][CH2:4][CH2:5][O:1]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 705192-Chloro-5-nitroanisoleHCID 119895722-(Oxolan-2-yl)ethan-1-ol

Product 1

HCID 672145772-(2-(2-Methoxy-4-nitrophenoxy)ethyl)tetrahydrofuranYield 73%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

To a solution of 2-(tetrahydrofuran-2-yl)ethanol (1.0 g, 8.61 mmol), prepared following the procedure as described in Synthesis, 594 (1996), in 15 mL of DMSO was added NaH (344 mg, 8.61 mmol, 60% in mineral oil) in portions. After the resulting suspension was stirred for 15 min., a solution of 1-chloro-2-methoxy-4-nitrobenzene in 5 mL of DMSO was added dropwise. The reaction mixture was stirred overnight, quenched with 15 mL of H2O, and extracted with EtOAc (3×30 mL). The organic layers were combined, dried over Na2SO4, and conc. in vacuo to yield a brown oil. The oil was purified by column chromatography (silica gel, 0%-35% gradient elution with EtOAc/hexanes) to yield 1.68 g (73%) of 2-(2-(2-methoxy-4-nitrophenoxy)ethyl)tetrahydrofuran as a yellow solid. MS (ESI) 268 (M+H)+. Subsequent conversion of the aryl nitro substituent to the title aryl amine was accomplished in 98% yield, following the procedure described in Example 6 step C. MS (ESI) 238 (M+H)+.

Workup

  1. stirringThe reaction mixture was stirred overnight
  2. customquenched with 15 mL of H2O
  3. extractionextracted with EtOAc (3×30 mL)
  4. dry with materialdried over Na2SO4
  5. customconc. in vacuo to yield a brown oil
  6. customThe oil was purified by column chromatography (silica gel, 0%-35% gradient elution with EtOAc/hexanes)

Sources & evidence

ORD record
ord-99821a0de91c4892be9358f167bc92f5
Source dataset
uspto-grants-2011_06
Patent number
US07956049B2

Reaction notes

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