2,5-Difluorobenzaldehyde → HCID 23114720, compound

HRID 2080369Notes

Reaction equation

HRID 2080369 reaction equation
C([Li])CCC.[Si:6]([O:23][CH2:24][C:25]1[CH:26]=[N:27][CH:28]=[C:29]([F:31])[CH:30]=1)([C:19]([CH3:22])([CH3:21])[CH3:20])([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[F:32][C:33]1[CH:40]=[CH:39][C:38]([F:41])=[CH:37][C:34]=1[CH:35]=[O:36].C(=O)(O)[O-].[Na+]>CCCCCC.O.C(OCC)C>[Si:6]([O:23][CH2:24][C:25]1[CH:30]=[C:29]([F:31])[C:28]([CH:35]([C:34]2[CH:37]=[C:38]([F:41])[CH:39]=[CH:40][C:33]=2[F:32])[OH:36])=[N:27][CH:26]=1)([C:19]([CH3:21])([CH3:22])[CH3:20])([C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

8

Reactant 4

HCID 1376632,5-DifluorobenzaldehydeHCID 516892Sodium BicarbonateHCID 231147533-({[tert-Butyl(diphenyl)silyl]oxy}methyl)-5-fluoropyridineHCID 178418339Butyllithium

Product 1

HCID 23114720HCID 23114720, compoundYield 79%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×HCID 8058HexaneSolvent2×

Conditions

Temperature
-20 °C

Procedure

At −78° C., a hexane solution (30.0 ml, 46.8 mmol) of n-butyl lithium and N,N,N′N′-tetramethylethylenediamine (7.06 ml, 46.8 mmol) were added sequentially to diethyl ether (250 ml). After stirring at −20° C. for 30 minutes, the reaction mixture was cooled to −78° C., and a diethyl ether (50 ml) solution of 3-(t-butyldiphenylsilyloxymethyl)-5-fluoropyridine (15.5 g, 42.5 mmol) was added thereto. The resulting mixture was stirred at the same temperature for 30 minutes. To the reaction mixture was added 2,5-difluorobenzaldehyde (6.04 g, 42.5 mmol). The resulting mixture was stirred for 2 hours. Water and then, a saturated aqueous solution of sodium bicarbonate were added to the reaction mixture. The resulting mixture was extracted with diethyl ether. The organic layer was dried over anhydrous sodium sulfate and then, filtered. The filtrate was concentrated under reduced pressure. The residue thus obtained was subjected to flash silica gel chromatography. The fraction obtained from the hexane:ethyl acetate=9:1 eluate was concentrated under reduced pressure to give the title compound (17.0 g, 33.5 mmol, 79%) as a colorless oil.

Workup

  1. temperaturethe reaction mixture was cooled to −78° C.
  2. stirringThe resulting mixture was stirred at the same temperature for 30 minutes
  3. stirringThe resulting mixture was stirred for 2 hours
  4. extractionThe resulting mixture was extracted with diethyl ether
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customThe residue thus obtained
  9. concentrationethyl acetate=9:1 eluate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-5af5e15fca2e49a9b291d46987c3d020
Source dataset
uspto-grants-2011_04
Patent number
US07932271B2

Reaction notes

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