2-Chloromethyl tetrahydrofuran → HCID 70225231, compound

HRID 1532857Notes

Reaction equation

HRID 1532857 reaction equation
[OH:1][CH2:2][C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[C:5]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:4]=1.[CH2:19](Cl)[CH:20]1[O:24][CH2:23][CH2:22][CH2:21]1.[H-].[Na+]>CN(C=O)C.[N+](CCCC)(CCCC)(CCCC)CCCC.[Br-]>[CH3:10][O:9][C:7](=[O:8])[C:6]1[CH:11]=[CH:12][C:3]([CH2:2][O:1][CH2:19][CH:20]2[CH2:21][CH2:22][CH2:23][O:24]2)=[CH:4][C:5]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 3

HCID 181502-Chloromethyl tetrahydrofuranHCID 24758Sodium hydrideHCID 10824066Methyl 4-hydroxymethyl-2-phenylbenzoate

Product 1

HCID 70225231HCID 70225231, compoundYield 2.9%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

A solution of 4-hydroxymethyl-2-phenylbenzoic acid, methyl ester (1.94 g, 8.00 mmol), prepared as in Example 158C, and tetrahydrofurfuryl chloride (1.18 g, 9.60 mmol) in DMF (4 mL) was added to a mixture of NaH (6.40 g, 16.0 mmol) (rinsed with THF just prior to use), KI (1.33 g, 9.00 mmol), and Bu4NBr (2.60 g, 0.800 mmol). An exothermic reaction including gas evolution was observed. The mixture was stirred 30 minutes and then heated to 130° C. for 3.5 hours. The reaction mixture was quenched by the addition of a few drops of methanol and then treated with H2O. The mixture was extracted with 2:1 ether-ethyl acetate and ether (2×). The combined organic extracts were rinsed with H2O (4×) and chromatography eluting 20% ethyl acetate-hexane) afforded the desired compound (74.9 mg) as an oil shown to be 89% pure by 1H NMR.

Workup

  1. washrinsed with THF just
  2. customAn exothermic reaction
  3. customThe reaction mixture was quenched by the addition of a few drops of methanol
  4. additiontreated with H2O
  5. extractionThe mixture was extracted with 2:1 ether-ethyl acetate and ether (2×)
  6. washThe combined organic extracts were rinsed with H2O (4×) and chromatography
  7. washeluting 20% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-98f099942d3446c6871d57a6176d18a0
Source dataset
uspto-grants-2001_03
Patent number
US06204293B1

Reaction notes

Loading…