Benzyl Bromide → 2-[[3-[Hydroxymethyl]-7-oxabicyclo[2.2.1]hept-2-yl]methyl]-4-fluoro-1-phenylmethoxy-benzene

HRID 252231Notes

Reaction equation

HRID 252231 reaction equation
[OH:1][CH2:2][CH:3]1[CH:8]2[O:9][CH:5]([CH2:6][CH2:7]2)[CH:4]1[CH2:10][C:11]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:12]=1[OH:18].[OH-].[K+].[CH2:21](Br)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C(O)C>[OH:1][CH2:2][CH:3]1[CH:8]2[O:9][CH:5]([CH2:6][CH2:7]2)[CH:4]1[CH2:10][C:11]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:12]=1[O:18][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 14797Potassium Hydroxide2×HCID 597080222-[[3-[Hydroxymethyl]-7-oxabicyclo[2.2.1]hept-2-yl]methyl]-4-fluoro-phenol

Product 1

HCID 597080332-[[3-[Hydroxymethyl]-7-oxabicyclo[2.2.1]hept-2-yl]methyl]-4-fluoro-1-phenylmethoxy-benzeneYield 94.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of [1S-(1α, 2α, 3α, 4α)]-2-[[3-[hydroxymethyl]-7-oxabicyclo[2.2.1]hept-2-yl]methyl]-4-fluoro-phenol (0.71 g, 2.8 mmol) in ethanol (30 mL) was added potassium hydroxide (0.173 g, 3.08 mmol) and the resulting mixture was refluxed until the potassium hydroxide dissolved. Then benzyl bromide (0.332 mL, 2.8 mmol) was added and the reaction was left to reflux for 16 h. After this time, the reaction was stopped and the solvent was evaporated under vacuum. The crude product was partitioned between ethyl acetate (30 mL) and 2M HCl (15 mL). The organic phase was separated; washed with a sat. solution of sodium bicarbonate (15 mL), brine (15 mL), dried (MgSO4), filtered and the solvent was evaporated “under vacuum” to give the crude product as an oil. The crude product was purified by chromatography column on a 20G SPE cartridge using ethyl acetate/hexane 1:2 as eluent to isolate 0.906 g (94%) of titled product as an oil. 1H-NMR (CDCl3, 300 MHz) δ 7.37(m, 5H, ArH), 6.86 (m, 3H, ArH), 5.08 (s, 2H, —OCH2Ph), 4.56 (d, 1H, J=4.9 Hz, —CH—O—), 4.27 (d, 1H, J=4.9 Hz, —CH—O—), 3.74 (m, 2H, —CH2OH), 2.86 (dd, 1H, J=4.4, 13.9 Hz, —CH—), 2.53 (dd, 1H, J=11.3, 13.7 Hz, —CH—), 2.29 (m, 1H, —CH2—), 2.08 (m, 1H, —CH2—), 1.80-1-32 (m, 4H, —CH2—CH2—)

Workup

  1. dissolutiondissolved
  2. waitthe reaction was left
  3. temperatureto reflux for 16 h
  4. customthe solvent was evaporated under vacuum
  5. customThe crude product was partitioned between ethyl acetate (30 mL) and 2M HCl (15 mL)
  6. customThe organic phase was separated
  7. washwashed with a sat. solution of sodium bicarbonate (15 mL), brine (15 mL)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. customthe solvent was evaporated “under vacuum”
  11. customto give the crude product as an oil
  12. customThe crude product was purified by chromatography column on a 20G SPE cartridge

Sources & evidence

ORD record
ord-3a5330aebd8b4eb390bdc39927855d56
Source dataset
uspto-grants-2011_01
Patent number
US07868032B2

Reaction notes

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