Toluene → HCID 22004884, compound

HRID 324888Notes

Reaction equation

HRID 324888 reaction equation
[CH:1]([C:4]1[C:5]([CH2:24][C:25]([OH:27])=[O:26])=[C:6]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[C:7](CC(O)=O)=[C:8]([CH:10]([CH3:12])[CH3:11])[CH:9]=1)([CH3:3])[CH3:2].[H-].[CH3:29][O:30]CCO[Al+]OCCOC.[Na+].[H-].C1(C)C=CC=CC=1>O1CCCC1>[CH:10]([C:8]1[C:7]([CH2:29][OH:30])=[C:6]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[C:5]([CH2:24][C:25]([OH:27])=[O:26])=[C:4]([CH:1]([CH3:3])[CH3:2])[CH:9]=1)([CH3:11])[CH3:12]

Participants

5

Reactant 3

HCID 1140TolueneHCID 21584525Sodium bis(2-methoxyethoxy)aluminiumhydrideHCID 86756636HCID 86756636, compound

Product 1

HCID 22004884HCID 22004884, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the intermediate obtained in Step C (37.3 g, 100 mmol) in anhydrous tetrahydrofuran (350 mL) stirred under argon at 0° C. was added a solution of 3.4M of sodium bis(2-methoxyethoxy)aluminum hydride in toluene (Red-Al) (105 mL, 204 mmol, 65 wt % in toluene) via syringe over 20 min. The reaction mixture was allowed to stir at room temperature for 24 hr, then cooled again to 0° C. and carefully quenched by the dropwise addition of water. The solution was decanted from the solid which forms and the solvent removed in vacuo. The residue was purified by flash chromatography (500 g silica) via step gradient. Elution with 5% diethyl ether/hexane affords 9.8 g (26.3 mmol, 28%) of recovered starting material and elution with 40% diethyl ether (Et2O)/hexane affords the desired product as a white solid (26.8 g, 77.8 mmol, 78%). mp 124-126° C. Rf=0.2 (10% ethyl acetate/hexane). 1H NMR (300 MHz, CDCl3): δ 7.35 (s, 1H), 7.27 (m, 2H), 7.08 (m, 2H), 4.44 (d, J=5.5 Hz, 2H), 3.43 (m, 4H), 2.92 (sept, J=6.6 Hz, 1H), 1.59 (s, 1H), 1.28 (m, 12H). FAB-MS: calculated for (C21H25FO3) 344, found 345 (M+H).

Workup

  1. temperaturecooled again to 0° C.
  2. customcarefully quenched by the dropwise addition of water
  3. customThe solution was decanted from the solid which forms
  4. customthe solvent removed in vacuo
  5. customThe residue was purified by flash chromatography (500 g silica) via step gradient
  6. washElution with 5% diethyl ether/hexane
  7. customaffords 9.8 g (26.3 mmol, 28%)
  8. customof recovered
  9. washmaterial and elution with 40% diethyl ether (Et2O)/hexane

Sources & evidence

ORD record
ord-d85e2cd9462e48a3bcb53374930fcad2
Source dataset
uspto-grants-2001_04
Patent number
US06218431B1

Reaction notes

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