Benzyl Bromide → 1-(S)-Benzyloxymethyl-2-(S)-(3-fluorophenyl)-4-methylenecyclopentane

HRID 8778Notes

Reaction equation

HRID 8778 reaction equation
[OH:1][CH2:2][C@@H:3]1[CH2:7][C:6](=[CH2:8])[CH2:5][C@H:4]1[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([F:15])[CH:10]=1.[CH2:16](Br)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[H-].[Na+]>CN(C=O)C.CCOCC>[CH2:16]([O:1][CH2:2][C@H:3]1[CH2:7][C:6](=[CH2:8])[CH2:5][C@@H:4]1[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([F:15])[CH:10]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 23548915(+)-trans-1-Hydroxymethyl-4-methylene-2-(3-fluorophenyl)cyclopentane

Product 1

HCID 235489111-(S)-Benzyloxymethyl-2-(S)-(3-fluorophenyl)-4-methylenecyclopentaneYield 90.4%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (+)-trans-1-hydroxymethyl-4-methylene-2-(3-fluorophenyl)cyclopentane (5.0 g, 26.5 mmol) from Example 1, Step C and benzyl bromide (4.7 mL, 40 mmol) in DMF (130 mL) was added 60% sodium hydride in mineral oil (0.77 g, 32 mmol). The reaction was stirred at room temperature for 24 h was then diluted with ether and slowly quenched into aq. sodium bicarbonate. After three ether extractions, the organic layers were combined, washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by FC (2–5% ethyl acetate in hexanes) to afford the title compound (7.1 g).

Workup

  1. customslowly quenched into aq. sodium bicarbonate
  2. extractionAfter three ether extractions
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by FC (2–5% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-f4f5c73c0baa450b83cabe4ac2020d77
Source dataset
uspto-grants-2006_08
Patent number
US07091211B2

Reaction notes

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