Sodium hydride → HCID 22050731, compound

HRID 1867160Notes

Reaction equation

HRID 1867160 reaction equation
[Br:1][C:2]1[C:3](=[O:19])[NH:4][C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].[H-].[Na+].[CH3:22][O:23][C:24]([C:26]1[O:27][C:28]([CH2:31]Cl)=[CH:29][CH:30]=1)=[O:25].C(#N)C.O>C1COCC1.[Cl-].[NH4+].O>[Br:1][C:2]1[C:3](=[O:19])[N:4]([CH2:31][C:28]2[O:27][C:26]([C:24]([O:23][CH3:22])=[O:25])=[CH:30][CH:29]=2)[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17]

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 75065Methyl 5-(chloromethyl)-2-furoateHCID 18373917Acetonitrile--water (1/1)HCID 220504293-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin-2(1H)-one

Product 1

HCID 22050731HCID 22050731, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
68 °C

Procedure

To a room temperature suspension of 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin-2(1H)-one (330.1 mg, 1.00 mmol)) and NaH (48.0 mg, 2.0 mmol) in THF (1.6 mL) was added methyl-5-chloromethyl-2-furate (400 mg, 2.30 mmol). The resulting suspension was stirred and heated to 68° C. for 8 hours until complete consumption of starting material by LCMS analysis. The reaction mixture was then diluted with ammonium chloride (saturated aqueous solution, 10 mL) and water (100 mL). This resulting emulsion was then extracted with ethyl acetate (3×300 mL). The resulting organic extract was separated, Na2SO4 dried, and concentrated. The resulting dark residue was subjected to SiO2 chromatography with ethyl acetate/hexanes (3:7) to furnish a solid. 1H NMR (400 MHz, CDCl3) δ 7.53 (app q, J=8.2 Hz, 1H), 7.07 (d, J=3.5 Hz, 1H), 6.93 (app dt, J=8.4, 1.5 Hz, 1H), 6.84 (app ddd, J=10.2, 8.7, 2.4 Hz, 1H), 6.53 (d, J=3.4 Hz, 1H), 6.00 (s, 1H), 5.27 (s, 2H), 5.18 (s, 2H), 3.85 (s, 3H), 2.54 (s, 3H); LC/MS C-18 column, tr=2.64 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50° C.). ES-MS m/z 468 (M+H). ES-HRMS m/z 468.0276 (M+H calcd for C20H17BrF2NO5 requires 468.0253).

Workup

  1. extractionThis resulting emulsion was then extracted with ethyl acetate (3×300 mL)
  2. extractionThe resulting organic extract
  3. customwas separated
  4. dry with materialNa2SO4 dried
  5. concentrationconcentrated
  6. customto furnish a solid

Sources & evidence

ORD record
ord-53e80de91cd349e8869090665426a829
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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