Benzyl Bromide → HCID 118194669, compound

HRID 1770371Notes

Reaction equation

HRID 1770371 reaction equation
[CH3:1][O:2][C:3]1[CH:22]=[CH:21][C:6]([CH2:7][O:8][C@H:9]([C@H:11]([CH2:16][CH2:17][CH:18]([CH3:20])[CH3:19])[C@@H:12]([OH:15])[CH:13]=[CH2:14])[CH3:10])=[CH:5][CH:4]=1.[H-].[Na+].[CH2:25](Br)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>CN(C=O)C>[CH2:25]([O:15][C@H:12]([C@@H:11]([CH2:16][CH2:17][CH:18]([CH3:19])[CH3:20])[C@@H:9]([O:8][CH2:7][C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:22][CH:21]=1)[CH3:10])[CH:13]=[CH2:14])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 118194655HCID 118194655, compound

Product 1

HCID 118194669HCID 118194669, compoundYield 91%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (3S,4R)-4-((S)-1-((4-methoxybenzyl)oxy)ethyl)-7-methyloct-1-en-3-ol (2.34 g, 7.64 mmol) in DMF (15.3 mL) was added NaH (0.611 g, 15.3 mmol, 60% dispersion in mineral oil) at 0° C. After 20 min, benzyl bromide (2.27 mL, 19.1 mmol) was added and the reaction was stirred at 0° C. for 20 min, warmed to 45° C., and stirred at this temperature for 16 h. The reaction was cooled to room temperature and quenched with sat. aq. NH4Cl (40 mL). The mixture was extracted with Et2O (3×50 mL), and the combined organics were washed with brine (40 mL), dried over Na2SO4, filtered, and concentrated to dryness. The residue was purified using flash column chromatography (120 g SiO2, 0→20% EtOAc/hexanes) to afford the title compound (2.75 g, 6.93 mmol, 91%) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.38-7.34 (m, 2H), 7.32-7.25 (m, 3H), 7.22-7.17 (m, 2H), 6.87-6.78 (m, 2H), 5.78 (ddd, J=17.4, 9.9, 7.3 Hz, 1H), 5.27-5.18 (m, 2H), 4.58 (d, J=12.4 Hz, 1H), 4.42 (d, J=11.2 Hz, 1H), 4.29 (d, J=11.2 Hz, 1H), 4.26 (d, J=11.9 Hz, 1H), 4.04-3.96 (m, 1H), 3.77 (s, 3H), 3.64 (p, J=6.3 Hz, 1H), 1.73-1.63 (m, 1H), 1.55-1.42 (m, 2H), 1.43-1.21 (m, 3H), 1.15 (d, J=6.3 Hz, 3H), 0.86 (d, J=6.6 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ 158.92, 139.07, 137.94, 131.19, 129.17, 128.19, 127.77, 127.47, 116.82, 113.65, 81.13, 75.03, 70.36, 70.07, 55.22, 48.17, 38.66, 28.62, 23.67, 22.61, 16.84; ESIMS m/z 419 ([M+Na]+).

Workup

  1. temperaturewarmed to 45° C.
  2. stirringstirred at this temperature for 16 h
  3. temperatureThe reaction was cooled to room temperature
  4. customquenched with sat. aq. NH4Cl (40 mL)
  5. extractionThe mixture was extracted with Et2O (3×50 mL)
  6. washthe combined organics were washed with brine (40 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. customThe residue was purified

Sources & evidence

ORD record
ord-92062f04815f42ab827bd6f79c0d1be4
Source dataset
uspto-grants-2016_02
Patent number
US09247741B2

Reaction notes

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