Hexane → 2-Fluoro-1,3-bis(methoxymethoxy)-4-methyl-benzene

HRID 1484516Notes

Reaction equation

HRID 1484516 reaction equation
[CH3:1][O:2][CH2:3][O:4][C:5]1[CH:10]=[C:9]([O:11][CH2:12][O:13][CH3:14])[CH:8]=[CH:7][C:6]=1[CH3:15].CCCCCC.C1(S(N([F:41])S(C2C=CC=CC=2)(=O)=O)(=O)=O)C=CC=CC=1>C1COCC1>[F:41][C:10]1[C:5]([O:4][CH2:3][O:2][CH3:1])=[C:6]([CH3:15])[CH:7]=[CH:8][C:9]=1[O:11][CH2:12][O:13][CH3:14]

Participants

5

Reactant 3

HCID 8058HexaneHCID 588007N-FluorobenzenesulfonimideHCID 679588332,4-Bis(methoxymethoxy)-1-methylbenzene2×

Product 1

HCID 727043342-Fluoro-1,3-bis(methoxymethoxy)-4-methyl-benzeneYield 89.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2,4-bis(methoxymethoxy)-1-methyl-benzene (WO2012/076877 Intermediate 150, 2000 mg, 9.4233 mmol) in dry THF (20 mL) butyllithium 1.6M in hexane (6.77 ml, 10.84 mmol) was slowly added and the reaction mixture was stirred for 30 minutes at room temperature. The reaction was cooled to −15° C. and it was added (via cannulation) to a solution of N-(benzenesulfonyl)-N-fluoro-benzenesulfonamide (3565.8 mg, 11.308 mmol) in dry THF (10 mL) at −15° C. The reaction mixture was stirred for 30 minutes at the same temperature. The reaction was quenched with brine (5 ml) diluted with water (20 ml) and extracted with ethyl acetate (2×30 ml). The organic layer was dried (Na2SO4), filtered and evaporated and the residue was purified by flash chromatography (Biotage system) on silica gel using a SNAP 50 g as column and cyclohexane/ethyl acetate from 100:0 to 80:20 as eluent affording the title compound (1950 mg) as colourless oil.

Workup

  1. temperatureThe reaction was cooled to −15° C.
  2. stirringThe reaction mixture was stirred for 30 minutes at the same temperature
  3. customThe reaction was quenched with brine (5 ml)
  4. additiondiluted with water (20 ml)
  5. extractionextracted with ethyl acetate (2×30 ml)
  6. dry with materialThe organic layer was dried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated
  9. customthe residue was purified by flash chromatography (Biotage system) on silica gel using a SNAP 50 g as column and cyclohexane/ethyl acetate from 100:0 to 80:20 as eluent

Sources & evidence

ORD record
ord-116cfff35a77435c945a50157d9d19f7
Source dataset
uspto-grants-2016_08
Patent number
US09422252B2

Reaction notes

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