Benzyl Bromide → HCID 18005882, compound

HRID 989283Notes

Reaction equation

HRID 989283 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[OH:12])[O:8][CH:7]([C:13]([O:15][CH2:16]C)=[O:14])[CH2:6][CH2:5]2.[H-].[Na+].[CH2:20](Br)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C1COCC1>[CH2:20]([O:12][C:11]1[CH:10]=[C:9]2[C:4]([CH2:5][CH2:6][CH:7]([C:13]([O:15][CH3:16])=[O:14])[O:8]2)=[CH:3][C:2]=1[Cl:1])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 18005866HCID 18005866, compound

Product 1

HCID 18005882HCID 18005882, compoundYield 6.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of ethyl 6-chloro-7-hydroxychroman-2-carboxylate (3.0 g, 11.7 mmol) in THF is treated with NaH (3.0 equiv, 35 mmol) at 0° C., stirred for 20 minutes, treated with benzylbromide (3.0 g, 17.5 mmol), stirred for 16 hr, concentrated and diluted with water and EtOAc. The aqueous phase is separated, acidified to pH 1-2 with 2N HCl and extracted with EtOAc. The extracts are combined, dried over MgSO4 and concentrated in vacuo. The resultant residue is dissolved in methanol, treated with a catalytic amount of p-toluenesulfonic acid, heated at reflux temperature for 18 hr, cooled and concentrated in vacuo. This resultant residue is triturated under EtOAc/hexanes and filtered. The filtercake is further purified by short-column chromatography (silica gel, 5:1 hexane:EtOAc as eluent) to afford the title product as a light yellow solid, 2.7 g (6.9% yield), identified by NMR and mass spectral analyses.

Workup

  1. stirringstirred for 16 hr
  2. concentrationconcentrated
  3. additiondiluted with water and EtOAc
  4. customThe aqueous phase is separated
  5. extractionextracted with EtOAc
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. dissolutionThe resultant residue is dissolved in methanol
  9. additiontreated with a catalytic amount of p-toluenesulfonic acid
  10. temperatureheated
  11. temperatureat reflux temperature for 18 hr
  12. temperaturecooled
  13. concentrationconcentrated in vacuo
  14. customThis resultant residue is triturated under EtOAc/hexanes
  15. filtrationfiltered
  16. customThe filtercake is further purified by short-column chromatography (silica gel, 5:1 hexane:EtOAc as eluent)

Sources & evidence

ORD record
ord-63c147b2fbc4415ead82ff5f7bf0c4af
Source dataset
uspto-grants-2003_10
Patent number
US06638972B2

Reaction notes

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