Sodium hydride → [(R)-2-(2,2-diethoxyethoxy)-4-pentenyloxymethyl]benzene

HRID 1427382Notes

Reaction equation

HRID 1427382 reaction equation
[CH2:1]([O:8][CH2:9][C@H:10]([OH:14])[CH2:11][CH:12]=[CH2:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:18][CH:19]([O:23][CH2:24][CH3:25])[O:20][CH2:21][CH3:22]>O1CCCC1>[CH2:21]([O:20][CH:19]([O:23][CH2:24][CH3:25])[CH2:18][O:14][C@H:10]([CH2:11][CH:12]=[CH2:13])[CH2:9][O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH3:22]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 74852Ethane, 2-bromo-1,1-diethoxy-2×HCID 10375318(2R)-1-(benzyloxy)pent-4-en-2-ol

Product 1

HCID 59281174[(R)-2-(2,2-diethoxyethoxy)-4-pentenyloxymethyl]benzene

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of (2R)-1-(benzyloxy)pent-4-en-2-ol (C1) (material from the previous step, ≦60 mmol) in tetrahydrofuran (50 mL) was added drop-wise to a suspension of sodium hydride (60% in mineral oil, 11.0 g, 275 mmol) in tetrahydrofuran (100 mL) at 0° C. After the reaction mixture had stirred for 30 minutes at this temperature, a solution of 2-bromo-1,1-diethoxyethane (97%, 13.3 mL, 85.8 mmol) in tetrahydrofuran (50 mL) was added at 0° C., and the reaction mixture was heated at reflux for 18 hours. Additional 2-bromo-1,1-diethoxyethane (11 mL, 71 mmol) was added, and heating was continued for a further 24 hours. The reaction mixture was cooled to 0° C., quenched with water, and extracted three times with ethyl acetate. The combined organic layers were washed with water, washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. Chromatography on silica gel (Gradient: 0% to 15% ethyl acetate in heptane) afforded the product as a colorless oil. Yield: 11.04 g, 35.80 mmol, 60% over 2 steps. 1H NMR (400 MHz, CDCl3) δ 1.21 (t, J=7.1 Hz, 3H), 1.22 (t, J=7.0 Hz, 3H), 2.31-2.36 (m, 2H), 3.49-3.74 (m, 9H), 4.55 (s, 2H), 4.61 (t, J=5.3 Hz, 1H), 5.02-5.12 (m, 2H), 5.78-5.90 (m, 1H), 7.27-7.38 (m, 5H).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 18 hours
  3. temperatureheating
  4. waitwas continued for a further 24 hours
  5. customquenched with water
  6. extractionextracted three times with ethyl acetate
  7. washThe combined organic layers were washed with water
  8. washwashed with saturated aqueous sodium chloride solution
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9891d33fb47440b8b5af3260d1c9827f
Source dataset
uspto-grants-2015_01
Patent number
US08933221B2

Reaction notes

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