Tetrahydrofuran → HCID 20780529, compound

HRID 535153Notes

Reaction equation

HRID 535153 reaction equation
C1COCC1.[H-].[Al+3].[Li+].[H-].[H-].[H-].C([O:14][C:15](=O)[CH2:16][CH2:17][C:18]1([CH2:31][CH2:32][C:33](OCC)=[O:34])[C:30]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[C:24]2[C:19]1=[CH:20][CH:21]=[CH:22][CH:23]=2)C.[OH-].[Na+]>CCOCC.CCOCC.C1COCC1.O>[OH:14][CH2:15][CH2:16][CH2:17][C:18]1([CH2:31][CH2:32][CH2:33][OH:34])[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:24]=2[C:25]2[C:30]1=[CH:29][CH:28]=[CH:27][CH:26]=2

Participants

8

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 14798Sodium HydroxideHCID 337679,9-Fluorenedipropionic acid, diethyl esterHCID 21226445Aluminium lithium hydride2×

Product 1

HCID 20780529HCID 20780529, compoundYield 87.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 3283Diethyl EtherSolvent4×HCID 21868444Ether tetrahydrofuranSolvent

Procedure

A 2-neck 1-Liter round bottom flask was equipped with a condenser, a magnetic stir bar and an addition funnel. The flask was charged with 15 mL of anhydrous THF and 30 mL of anhydrous ether. Lithium aluminum hydride (4.80 g) was then carefully added to the flask. 3-[9-(2-Ethoxycarbonyl-ethyl)-9H-fluoren-9-yl]-propionic acid ethyl ester (18.2 g) was dissolved in 95 mL of anhydrous ether and 37 mL of anhydrous THF and this mixture was added to the addition funnel. The solution of diester was then added dropwise to the rapidly stirred lithium aluminum hydride suspension over a period of 60 min. After an additional 2 hours, the rapidly stirred reaction mixture was carefully treated by the dropwise addition of water (31 mL), followed by 35% NaOH solution (63 mL), and finally more water (66 mL). Additional diethyl ether was added to keep the slurry stirring. After stirring for 30 min, the ether/THF layer was allowed to separate and was then decanted from the aluminum salts. The salts were rinsed with additional portions of diethyl ether. The combined organic portions were concentrated under reduced pressure to give a white solid. The white solid was dissolved in 200 mL of ether and 100 mL of THF, washed with 1N HCl solution (2×75 mL) and brine. The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The resulting white solid was crystallized from hot toluene to give the title compound (1-c) (12.3 g) as white flakes. 1H NMR (CDCl3, 500 MHz) δ 7.71 (m, 2H), 7.37-7.27 (m, 6H), 3.32 (t, J=6.4 Hz, 4H), 2.09 (m, 4H), 0.87 (m, 4H).

Workup

  1. customA 2-neck 1-Liter round bottom flask was equipped with a condenser, a magnetic stir bar and an addition funnel
  2. customthe rapidly stirred reaction mixture
  3. stirringAfter stirring for 30 min
  4. customto separate
  5. customwas then decanted from the aluminum salts
  6. washThe salts were rinsed with additional portions of diethyl ether
  7. concentrationThe combined organic portions were concentrated under reduced pressure
  8. customto give a white solid
  9. wash100 mL of THF, washed with 1N HCl solution (2×75 mL) and brine
  10. dry with materialThe organic layer was dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe resulting white solid was crystallized from hot toluene

Sources & evidence

ORD record
ord-45b337e8134f4d7daa183b9e1dedb8cb
Source dataset
uspto-grants-2014_10
Patent number
US08854730B2

Reaction notes

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