Sodium hydride → 4-(3-Tetrahydrofurylmethyloxymethyl)-2-phenylbenzoic acid methyl ester

HRID 1532855Notes

Reaction equation

HRID 1532855 reaction equation
[CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10]Cl)=[CH:6][C:5]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[O:19]1[CH2:23][CH2:22][CH:21]([CH2:24][OH:25])[CH2:20]1.[H-].[Na+]>CN(C=O)C.[N+](CCCC)(CCCC)(CCCC)CCCC.[Br-]>[CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][O:25][CH2:24][CH:21]2[CH2:22][CH2:23][O:19][CH2:20]2)=[CH:6][C:5]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 139980Tetrahydro-3-furanmethanolHCID 544945664-Chloromethyl-2-phenylbenzoic acid methyl ester

Product 1

HCID 702254664-(3-Tetrahydrofurylmethyloxymethyl)-2-phenylbenzoic acid methyl ester

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

A solution of the product of Example 287A (2.09 g, 8.00 mmol) and tetrahydro-3-furanmethanol (0.990 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 for 30 minutes and then heated at 130° C. for 3.5 hours. The reaction mixture was quenched with by the addition of a few drops of methanol and then treated with H2O (50 mL). The mixture was extracted with a 2:1 mixture of ether and ethyl acetate, followed by ether (2×). The combined organic extracts were rinsed with H2O (4×) and brine, dried (MgSO4), and concentrated under reduced pressure. Flash column chromatography (20% ethyl acetate-hexane) afforded 0.406 g (14.5%) of a 1.6:1 mixture of the methyl and tetrahydro-3-furanmethyl esters, respectively.

Workup

  1. washrinsed with THF just
  2. customAn exothermic reaction
  3. customThe reaction mixture was quenched with by the addition of a few drops of methanol
  4. additiontreated with H2O (50 mL)
  5. extractionThe mixture was extracted with a 2:1 mixture of ether and ethyl acetate
  6. washThe combined organic extracts were rinsed with H2O (4×) and brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated under reduced pressure
  9. customFlash column chromatography (20% ethyl acetate-hexane) afforded

Sources & evidence

ORD record
ord-ab834d8c147945f88eb0006bd40ebf66
Source dataset
uspto-grants-2001_03
Patent number
US06204293B1

Reaction notes

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