Cornforth reagent → HCID 23116292, compound

HRID 495312Notes

Reaction equation

HRID 495312 reaction equation
[CH3:1][C:2]1([CH3:38])[O:6][CH:5]([CH2:7][O:8][CH2:9][CH2:10][C:11]2[C:16]([CH:17]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([F:27])[CH:20]=3)[OH:18])=[C:15]([O:28][CH2:29][O:30][CH3:31])[CH:14]=[C:13]([O:32][CH2:33][O:34][CH3:35])[C:12]=2[CH2:36][CH3:37])[CH2:4][O:3]1.[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=O.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1>ClCCl.C(OCC)C>[F:27][C:21]1[CH:20]=[C:19]([C:17]([C:16]2[C:11]([CH2:10][CH2:9][O:8][CH2:7][CH:5]3[CH2:4][O:3][C:2]([CH3:1])([CH3:38])[O:6]3)=[C:12]([CH2:36][CH3:37])[C:13]([O:32][CH2:33][O:34][CH3:35])=[CH:14][C:15]=2[O:28][CH2:29][O:30][CH3:31])=[O:18])[CH:24]=[CH:23][C:22]=1[O:25][CH3:26]

Participants

5

Reactant 2

HCID 2724130Cornforth reagentHCID 23116506HCID 23116506, compound

Product 1

HCID 23116292HCID 23116292, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

2-Bromo-3-{2-[(2,2-dimethyl-1,3-dioxolan-4-yl)methoxy]ethyl}-4-ethyl-1,5-bis(methoxymethoxy)benzene (390 mg, 0.84 mmol) obtained in the step 3 in Example 173 was dissolved in tetrahydrofuran (10 mL), and with stirring at −78° C., tetrahydrofuran solution of 1.5 mol/L n-butyllithium (1.0 mL, 1.5 mmol) was dropwise added thereto. The resulting mixture was stirred at −78° C. for 30 minutes, then 2-fluoro-4-methoxybenzaldehyde (130 mg, 0.8 mmol) was dropwise added thereto and further stirred for 30 minutes. Aqueous saturated ammonium chloride solution was added to the reaction mixture, and extracted twice with ethyl acetate. The organic layers were combined, washed with aqueous saturated sodium chloride solution, then dried over anhydrous sodium sulfate, and the solvent was evaporated away to obtain 1-(6-{2-[(2,2-dimethyl-1,3-dioxolan-4-yl)methoxy]ethyl}-5-ethyl-2,4-bis(methoxymethoxy)phenyl)-1-(3-fluoro-4-methoxyphenyl)methanol. Thus obtained, 1-(6-{2-[(2,2-dimethyl-1,3-dioxolan-4-yl)methoxy]ethyl}-5-ethyl-2,4-bis(methoxymethoxy)phenyl)-1-(3-fluoro-4-methoxyphenyl)methanol was dissolved in dichloromethane (10 mL), and pyridinium dichromate (160 m, 0.43 mmol) was added thereto and stirred at room temperature for 8 hours. The reaction mixture was diluted with diethyl ether, filtered through Celite, and the filtrate was concentrated under reduced pressure. The resulting residue was purified through silica gel column chromatography (ethyl acetate/hexane=1/4 to 1/1) to obtain 6-{2-[(2,2-dimethyl-1,3-dioxolan-4-yl)methoxy]ethyl}-5-ethyl-2,4-bis(methoxymethoxy)phenyl 3-fluoro-4-methoxyphenyl ketone (210 mg, 46%).

Workup

  1. customThus obtained
  2. filtrationfiltered through Celite
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customThe resulting residue was purified through silica gel column chromatography (ethyl acetate/hexane=1/4 to 1/1)

Sources & evidence

ORD record
ord-2c7666887ac84ce3921d5e983f7ca3ed
Source dataset
uspto-grants-2009_05
Patent number
US07538241B2

Reaction notes

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