1,2-Dibromoethane → HCID 66771044, compound

HRID 1697758Notes

Reaction equation

HRID 1697758 reaction equation
COC(=O)CC1C2C(=CC=CC=2)C(Br)=CC=1.C([N-]C(C)C)(C)C.[Li+].BrCCBr.C[O:30][C:31](=[O:47])[CH:32]([C:36]1[C:45]2[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=2)[C:39]([Br:46])=[CH:38][CH:37]=1)[CH2:33][CH2:34]Br.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.O1CCCC1.CCCCCCC.C(C1C=CC=CC=1)C.CN(C)P(N(C)C)(N(C)C)=O>[Br:46][C:39]1[C:40]2[C:45](=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:36]([C:32]2([C:31]([OH:30])=[O:47])[CH2:34][CH2:33]2)=[CH:37][CH:38]=1

Participants

9

Reactant 5

HCID 78391,2-DibromoethaneHCID 11430Potassium CarbonateHCID 2724682Lithium diisopropylamideHCID 22711823HCID 22711823, compoundHCID 66770812HCID 66770812, compound

Product 1

HCID 66771044HCID 66771044, compoundYield 30%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 12679HexamethylphosphoramideSolventHCID 22742125Tetrahydrofuran heptane ethylbenzolSolvent

Procedure

To a solution of (4-Bromo-naphthalen-1-yl)-acetic acid methyl ester (Example 472a), 687 mg) in tetrahydrofuran (13 mL) and Hexamethylphosphoramide (1.3 mL) was added at −78° C. a solution of lithiumdiisopropylamide (2M, 2.71 mL) in tetrahydrofuran/heptane/ethylbenzene within 5 min. 1,2-dibromoethane (695 mg) was added rapidly and the reaction mixture was stirred at room temperature for 3 hr. The reaction mixture was concentrated under vacuo and the residue partitioned between ethylacetate and a saturated aqueous solution of ammonium chloride. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with water and brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford a crude mixture containing 4-Bromo-2-(4-bromo-naphthalen-1-yl)-butyric acid methyl ester. This crude material was dissolved in tetrahydrofuran (13 mL) at room temperature and potassium carbonate (692 mg) was added. The mixture was stirred at room temperature for 36 hr, concentrated under vacuo, partitioned between ethyl acetate and a hydrochloric acid (0.1N). The aqueous layer was extracted with ethyl acetate and the combined organic layers were concentrated in vacuo. The crude mixture was concentrated to dryness and purified by chromatography on silica gel to yield the title compound as a colorless oil (215 mg; 30%). MS (ESI): m/z=290 [M−H]−.

Workup

  1. concentrationThe reaction mixture was concentrated under vacuo
  2. customthe residue partitioned between ethylacetate
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. washthe combined organic layers were washed with water and brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford a crude mixture
  9. stirringThe mixture was stirred at room temperature for 36 hr
  10. concentrationconcentrated under vacuo
  11. custompartitioned between ethyl acetate
  12. extractionThe aqueous layer was extracted with ethyl acetate
  13. concentrationthe combined organic layers were concentrated in vacuo
  14. concentrationThe crude mixture was concentrated to dryness
  15. custompurified by chromatography on silica gel

Sources & evidence

ORD record
ord-3c7a9870320f4e8b911ea729568bb925
Source dataset
uspto-grants-2012_04
Patent number
US08163793B2

Reaction notes

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