2,5-Difluorobenzaldehyde → 2-[(t-Butyldimethylsilyloxy)methyl]-4-[(2,5-difluorophenyl)hydroxymethyl]-5-methylpyridine

HRID 2080479Notes

Reaction equation

HRID 2080479 reaction equation
C([Li])CCC.Br[C:7]1[C:12]([CH3:13])=[CH:11][N:10]=[C:9]([CH2:14][O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[CH:8]=1.[F:23][C:24]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:25]=1[CH:26]=[O:27]>CCCCCC.O.C(OCC)C>[Si:16]([O:15][CH2:14][C:9]1[CH:8]=[C:7]([CH:26]([C:25]2[CH:28]=[C:29]([F:32])[CH:30]=[CH:31][C:24]=2[F:23])[OH:27])[C:12]([CH3:13])=[CH:11][N:10]=1)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17]

Participants

7

Reactant 3

HCID 1376632,5-DifluorobenzaldehydeHCID 231148234-Bromo-2-[(t-butyldimethylsilyloxy)methyl]-5-methylpyridineHCID 178418339Butyllithium

Product 1

HCID 231147292-[(t-Butyldimethylsilyloxy)methyl]-4-[(2,5-difluorophenyl)hydroxymethyl]-5-methylpyridineYield 74.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8058HexaneSolvent2×

Procedure

Under an argon atmosphere, n-butyl lithium (a 1.58M hexane solution, 400 μl, 0.632 mmol) was added to a diethyl ether (3 ml) solution of 4-bromo-2-[(t-butyldimethylsilyloxy)methyl]-5-methylpyridine (200 mg, 0.632 mmol) at −78° C. The resulting mixture was stirred for 1 hour. After 2,5-difluorobenzaldehyde (69 μl, 0.632 mmol) was added dropwise, the reaction mixture was stirred for 1 hour. To the reaction mixture were added water and a saturated aqueous solution of sodium bicarbonate, followed by extraction with diethyl ether. The extract was washed with brine. The organic layer thus obtained was dried over magnesium sulfate, and concentrated under reduced pressure. The residue thus obtained was subjected to flash silica gel column chromatography. The fraction obtained from the hexane:ethyl acetate=2:1 eluate was concentrated under reduced pressure to give the title compound (178 mg, 0.469 mmol, 74%) as a white powder.

Workup

  1. stirringthe reaction mixture was stirred for 1 hour
  2. extractiona saturated aqueous solution of sodium bicarbonate, followed by extraction with diethyl ether
  3. washThe extract was washed with brine
  4. customThe organic layer thus obtained
  5. dry with materialwas dried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue thus obtained
  8. concentrationethyl acetate=2:1 eluate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-016ccfca7b324a2d99ff8b927bbfe0e3
Source dataset
uspto-grants-2011_04
Patent number
US07932271B2

Reaction notes

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