Water → HCID 23114195, compound

HRID 2376591Notes

Reaction equation

HRID 2376591 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C([Li])CCC.[CH:13]([C:15]1[C:23]2[O:22][C:21]([CH3:25])([CH3:24])[CH2:20][C:19]=2[C:18]([CH3:26])=[C:17]([NH:27][C:28](=[O:34])[CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C:16]=1[CH3:35])=[O:14].O>C(OCC)C.C1COCC1.CCCCCC.C(OCC)(=O)C>[OH:14][CH:13]([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1)[C:15]1[C:23]2[O:22][C:21]([CH3:24])([CH3:25])[CH2:20][C:19]=2[C:18]([CH3:26])=[C:17]([NH:27][C:28](=[O:34])[CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C:16]=1[CH3:35]

Participants

9

Reactant 4

HCID 962WaterHCID 79732-BromopyridineHCID 23113844HCID 23113844, compoundHCID 178418339Butyllithium

Product 1

HCID 23114195HCID 23114195, compoundYield 68.1%

Reagents, catalysts & solvents 4

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-bromopyridine (553 mg, 3.5 mmol) in diethyl ether (3.0 mL) was added dropwise at −70° C. under argon atmosphere n-butyllithium (1.6 M, hexane solution, 2.13 mL, 3.4 mmol) and the mixture was stirred for 30 minutes. To the reaction solution was added dropwise at −70° C. a solution of N-(7-formyl-2,2,4,6-tetramethyl-2,3-dihydro-1-benzofuran-5-yl)-3,3-dimethylbutanamide (317 mg, 1.0 mmol) obtained in Example 340 in THF (4.0 mL) and the mixture was stirred for 30 minutes, and then warmed to room temperature. Water was added to the reaction solution and the product was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=1:10), and then by silica gel column chromatography (ethyl acetate:hexane=1:1) to obtain 270 mg (yield: 68%) of the title compound. Melting point: 176-177° C. (ethyl acetate-hexane).

Workup

  1. stirringthe mixture was stirred for 30 minutes
  2. extractionthe product was extracted with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=1:10)

Sources & evidence

ORD record
ord-2ab5af5a3b754664a4f92794ae307e5b
Source dataset
uspto-grants-2008_12
Patent number
US07465815B2

Reaction notes

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