Sodium hydride → 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-1-(thien-2-ylmethyl)pyridin-2(1H)-one

HRID 1832077Notes

Reaction equation

HRID 1832077 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+].Cl[CH2:23][C:24]1[S:25][CH:26]=[CH:27][CH:28]=1.C(#N)C.O>C1COCC1.C(OCC)(=O)C.O>[Br:1][C:2]1[C:3](=[O:19])[N:4]([CH2:23][C:24]2[S:25][CH:26]=[CH:27][CH:28]=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 698302-(Chloromethyl)thiopheneHCID 18373917Acetonitrile--water (1/1)HCID 220504293-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin-2(1H)-one

Product 1

HCID 220508103-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-1-(thien-2-ylmethyl)pyridin-2(1H)-one

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
68 °C

Procedure

To a room temperature suspension of 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin-2(1H)-one (330.0 mg, 1.00 mmol)) and NaH (48.0 mg, 2.0 mmol) in THF (3.0 mL) was added 2-(chloromethyl)thiophene (461 mg, 3.97 mmol). The resulting suspension was stirred and heated to 68° C. for 12 hours until complete consumption of starting material by LCMS analysis. The reaction mixture was then diluted with ethyl acetate (400 mL), water washed (3×200 mL). The resulting organic extract was separated, Na2SO4 dried, and concentrated. The resulting dark residue was subjected to SiO2 chromatography with ethyl acetate/hexanes (4:6) to furnish a solid. 1H NMR (400 MHz, d4-MeOH) δ 7.58 (app q, J=8.2 Hz, 1H), 7.30 (app dd, J=5.1, 1.2 Hz, 1H), 7.05 (d, J=2.6 Hz, 1H), 7.01 (app t, J=8.1 Hz, 2H), 6.93 (dd, J=5.1, 3.4 Hz, 1H), 6.43 (s, 1H), 5.49 (s, 2H), 5.25 (s, 2H), 2.51 (s, 3H); LC/MS C-18 column, tr=2.74 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50° C.). ES-MS m/z 426 (M+H). ES-HRMS m/z 425.9936 (M+H calcd for C18H15BrF2NO2S requires 425.9969).

Workup

  1. washwashed (3×200 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-8a10d7597de94c578013e6cb4d380f3e
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

Loading…