Sodium hydride → HCID 21035375, compound

HRID 1832037Notes

Reaction equation

HRID 1832037 reaction equation
[H-].[Na+].[Br:3][C:4]1[C:5](=[O:21])[NH:6][C:7]([CH3:20])=[CH:8][C:9]=1[O:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=1[F:19].Br[CH2:23]/[CH:24]=[CH:25]/[C:26]([O:28][CH3:29])=[O:27]>C1COCC1>[Br:3][C:4]1[C:5](=[O:21])[N:6]([CH2:23]/[CH:24]=[CH:25]/[C:26]([O:28][CH3:29])=[O:27])[C:7]([CH3:20])=[CH:8][C:9]=1[O:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=1[F:19]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 53691752-Butenoic acid, 4-bromo-, methyl esterHCID 220504293-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin-2(1H)-one

Product 1

HCID 21035375HCID 21035375, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred suspension of NaH (277 mg, 11 mmol) in anhydrous THF (30 ml), which was cooled to 0° C., was slowly added 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin-2(1H)-one (3.3 g, 10 mmol). The resulting slurry was stirred for 15 min, after which methyl 4-bromocrotonate (1.4 ml, 12 mmol) was added to the reaction. The ice bath was removed and the reaction was heated to reflux for 16 h. The reaction was quenched by the addition of 1N NH4Cl. The layers were separated and the aqueous layer was extracted with CH2Cl2 (5×). The organics were combined, dried, and concentrated in vacuo. The crude yellowish material was then triturated with Et2O to give, after filtration and drying, 1.8 g (43%) of a white solid. 1H-NMR (DMSOd6/300 MHz) δ 7.65 (app q, J=8.7 hz, 1H), 7.36 (app dt, J=12.0, 3.0 hz, 1H); 7.17 (dt, J=8.4, 1.8 Hz, 1H); 6.94 (dt, J=15.9, 4.5 Hz, 1H); 6.57 (s, 1H), 5.52 (d, J=15.9 Hz, 1H), 5.29 (s, 2H), 4.84 (m, 2H), 3.63 (s, 3H), 2.33 (s, 3H). ES-HRMS m/z 428.0301 (M+H calcd for C18H17BrF2NO4=428.0310).

Workup

  1. customThe ice bath was removed
  2. temperaturethe reaction was heated
  3. temperatureto reflux for 16 h
  4. customThe reaction was quenched by the addition of 1N NH4Cl
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with CH2Cl2 (5×)
  7. customdried
  8. concentrationconcentrated in vacuo
  9. customThe crude yellowish material was then triturated with Et2O
  10. customto give
  11. filtrationafter filtration
  12. customdrying

Sources & evidence

ORD record
ord-3f40ff078a1649fca5ae5de22598ce76
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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