Dimethylformamide → HCID 117806047, compound

HRID 1410654Notes

Reaction equation

HRID 1410654 reaction equation
[CH3:1][C:2]1[C:11]([CH3:12])=[C:10]2[C:5]([CH2:6][CH2:7][C@:8]([CH2:14][CH2:15][CH2:16][C@@H:17]([CH2:19][CH2:20][CH2:21][C@@H:22]([CH2:24][CH2:25][CH2:26][CH:27]([CH3:29])[CH3:28])[CH3:23])[CH3:18])([CH3:13])[O:9]2)=[C:4]([CH3:30])[C:3]=1[OH:31].[H-].[Na+].[H][H].CN(C)[CH:38]=[O:39]>>[O:39]1[CH2:38][CH2:10][O:9][CH:8]1[CH2:7][CH2:6][CH2:5][CH2:4][O:31][C:3]1[C:4]([CH3:30])=[C:5]2[C:10](=[C:11]([CH3:12])[C:2]=1[CH3:1])[O:9][C@:8]([CH3:13])([CH2:14][CH2:15][CH2:16][C@H:17]([CH3:18])[CH2:19][CH2:20][CH2:21][C@H:22]([CH3:23])[CH2:24][CH2:25][CH2:26][CH:27]([CH3:29])[CH3:28])[CH2:7][CH2:6]2

Participants

5

Reactant 4

HCID 6228Dimethylformamide2×HCID 14985alpha-TocopherolHCID 24758Sodium hydrideHCID 178418361HCID 178418361, compound

Product 1

HCID 117806047HCID 117806047, compoundYield 86%

Procedure

To a stirred solution of (+)-α-tocopherol (1.54 g, 3.6 mmol, 1.1 equiv.) in N,N-dimethylformamide (DMF, 30 mL) at 0° C. (ice/water bath) was added NaH (60% in mineral oil, 0.30 g, 7.5 mmol, 2.2 equiv.) in a single portion. After hydrogen gas was no longer being visibly evolved, the cooling bath was removed, and the mixture stirred at room temperature for 1 h. A solution of tosylated compound of Step 5 (crude from previous step, assumed 3.4 mmol, 1.0 equiv) in DMF (10 mL) was added to the reaction mixture at room temperature. The mixture was stirred at 80° C. for 20 h. Solvent was removed by coevaporation with PhMe (3×50 mL). The residue was taken up in EtOAc (250 mL). The solution was then washed with sat. aq. NaHCO3 (50 mL) and brine (50 mL). The combined aqueous fractions were extracted with EtOAc (2×50 mL). The combined organic fractions were then dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, pet ether to EtOAc:pet ether=1:9) to give the resulting compound (1.65 g, 3.0 mmol, 86% yield) as colorless oil. XX: 1H NMR (500 MHz, CDCl3) δ=4.93 (t, J=4.7 Hz, 1H), 4.05-3.94 (m, 2H), 3.92-3.84 (m, 2H), 3.68 (t, J=6.6 Hz, 2H), 2.60 (t, J=6.9 Hz, 2H), 2.20 (s, 3H), 2.16 (s, 3H), 2.12 (s, 3H), 1.93-1.05 (m, 29H), 1.27 (s, 3H), 0.97-0.83 (m, 12H) ppm; 13C NMR (125 MHz, CDCl3) δ=148.6, 147.8, 127.9, 125.9, 122.9, 117.6, 104.7, 74.8, 72.9, 65.0, 40.3, 39.6, 37.67, 37.65, 37.6, 37.5, 34.1, 33.0, 32.9, 31.5, 30.4, 28.2, 25.0, 24.6, 24.1, 22.9, 22.8, 21.2, 21.0, 20.8, 19.94, 19.85, 12.9, 12.03, 11.9 ppm; HRMS (ESI+ve) m/z: 559.4719 ([M+H]+); C36H63O4 requires 559.4721.

Workup

  1. customthe cooling bath was removed
  2. stirringThe mixture was stirred at 80° C. for 20 h
  3. customSolvent was removed by coevaporation with PhMe (3×50 mL)
  4. washThe solution was then washed with sat. aq. NaHCO3 (50 mL) and brine (50 mL)
  5. extractionThe combined aqueous fractions were extracted with EtOAc (2×50 mL)
  6. dry with materialThe combined organic fractions were then dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash column chromatography (silica gel, pet ether to EtOAc:pet ether=1:9)

Sources & evidence

ORD record
ord-0e6e929c4f79435da6b0aca6a43ada09
Source dataset
uspto-grants-2014_12
Patent number
US08921568B2

Reaction notes

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