Benzyl Bromide → HCID 18922350, compound

HRID 1289975Notes

Reaction equation

HRID 1289975 reaction equation
[OH:1][CH:2]1[CH2:6][CH2:5][CH:4]([C:7]([O:9]C)=[O:8])[CH:3]1[C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1.[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[H-].[Na+]>CN(C=O)C.CCOCC>[CH2:18]([O:1][CH:2]1[CH2:6][CH2:5][CH:4]([C:7]([OH:9])=[O:8])[CH:3]1[C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 18404441HCID 18404441, compound

Product 1

HCID 18922350HCID 18922350, compoundYield 106.1%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 10.0 gm of methyl 3-(SR)-(hydroxy)-2-(RS)-(4-fluorophenyl)cyclopentane-1-(RS)-carboxylate prepared as in Example 32 (lower isomer) and 10.8 gm of benzyl bromide in 50 mL of DMF was added in portions over 30 min 2.0 gm of 60% NaH in mineral oil. The reaction was stirred for 2 h at room temperature and was then diluted with ether and quenched by slow addition to water containing 25 mL of 2N HCl. The mixture was extracted twice with ether and the organic layers were washed with a portion of brine, combined, dried over sodium sulfate and evaporated. By T.l.c. and NMR the crude product consisted of a mixture of desired benzylated starting material and dimer derived from transesterification. The crude product was taken up in 100 mL of methanol and 45 mL of 5N NaOH was added. The mixture was stirred at room temperature for 40 h residue was diluted with waste. The residue was diluted with water and extracted twice with ether and the ether layers washed with dilute NaOH. The combined aqueous layers were acidified with HCl (c) and extracted twice with ethyl acetate. The organic layers were washed with a portion of brine, combined, dried over sodium sulfate and evaporated to give 14 gm of title compound contaminated with some 3-(SR)-(hydroxy)-2-(RS)-(4-fluorophenyl)cyclopentane-1-(RS)-carboxylic acid. This could be further purified by flash chromatography eluting with 20% ethyl acetate in hexanes followed by 1% HOAc/20% ethyl acetate in hexanes. T.l.c. (1% HOAc/20% ethyl acetate in hexanes) Rf =0.4.

Workup

  1. customquenched by slow addition to water containing 25 mL of 2N HCl
  2. extractionThe mixture was extracted twice with ether
  3. washthe organic layers were washed with a portion of brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated
  6. additionand NMR the crude product consisted of a mixture
  7. addition45 mL of 5N NaOH was added
  8. stirringThe mixture was stirred at room temperature for 40 h residue
  9. additionwas diluted with waste
  10. additionThe residue was diluted with water
  11. extractionextracted twice with ether
  12. washthe ether layers washed with dilute NaOH
  13. extractionextracted twice with ethyl acetate
  14. washThe organic layers were washed with a portion of brine
  15. dry with materialdried over sodium sulfate
  16. customevaporated

Sources & evidence

ORD record
ord-eb7caf94c54341868a01985e633fe1df
Source dataset
uspto-grants-1998_05
Patent number
US05750549

Reaction notes

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