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

HRID 590591Notes

Reaction equation

HRID 590591 reaction equation
[H-].[Na+].[CH2:3]([O:10][CH2:11][C@H:12]([OH:16])[CH2:13][CH:14]=[CH2:15])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.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:16][C@H:12]([CH2:13][CH:14]=[CH2:15])[CH2:11][O:10][CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH3:22]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 74852Ethane, 2-bromo-1,1-diethoxy-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 8028TetrahydrofuranSolvent2×

Procedure

This reaction was carried out in two identical experiments. To a 0° C. suspension of sodium hydride (60% in mineral oil, 124.8 g, 3.12 mol) in tetrahydrofuran (1 L) was added a solution of (2R)-1-(benzyloxy)pent-4-en-2-ol (C1) (200 g, 1.04 mol) in tetrahydrofuran (500 mL). The reaction was stirred for 30 minutes at room temperature, whereupon 2-bromo-1,1-diethoxyethane (528 g, 2.68 mol) was added, and the reaction mixture was heated at reflux for 18 hours. The mixture was carefully quenched with water (2×300 mL) and the combined experiments were concentrated in vacuo. The aqueous residue was partitioned between ethyl acetate (5 L) and water (5 L). The organic layer was washed with saturated aqueous sodium chloride solution (5 L), dried, and concentrated. Purification via silica gel chromatography (Eluent: 20:1 petroleum ether/ethyl acetate) provided the product as a yellow oil. Yield: 300 g, 0.97 mol, 47%. 1H NMR (400 MHz, CDCl3) δ 7.26-7.37 (m, 5H), 5.78-5.90 (m, 1H), 5.01-5.13 (m, 2H), 4.61 (t, J=5.3 Hz, 1H), 4.55 (s, 2H), 3.48-3.74 (m, 9H), 2.30-2.36 (m, 2H), 1.22 (t, J=7.1 Hz, 3H), 1.21 (t, J=7.0 Hz, 3H).

Workup

  1. additionwas added
  2. temperaturethe reaction mixture was heated
  3. temperatureat reflux for 18 hours
  4. customThe mixture was carefully quenched with water (2×300 mL)
  5. concentrationthe combined experiments were concentrated in vacuo
  6. customThe aqueous residue was partitioned between ethyl acetate (5 L) and water (5 L)
  7. washThe organic layer was washed with saturated aqueous sodium chloride solution (5 L)
  8. customdried
  9. concentrationconcentrated
  10. customPurification via silica gel chromatography (Eluent: 20:1 petroleum ether/ethyl acetate)

Sources & evidence

ORD record
ord-32261a88f5b245b98b6bf6a8690958ca
Source dataset
uspto-grants-2016_01
Patent number
US09233981B1

Reaction notes

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