Potassium Carbonate → HCID 21035387, compound

HRID 1831911Notes

Reaction equation

HRID 1831911 reaction equation
[Br:1][C:2]1[C:3](=[O:17])[NH:4][CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=1.C([O-])([O-])=O.[K+].[K+].[C:24]([O:28][C:29](=[O:40])[NH:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([CH2:38]Br)[CH:33]=1)([CH3:27])([CH3:26])[CH3:25]>CN(C=O)C>[C:24]([O:28][C:29](=[O:40])[NH:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([CH2:38][N:4]2[CH:5]=[CH:6][C:7]([O:8][CH2:9][C:10]3[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=3)=[C:2]([Br:1])[C:3]2=[O:17])[CH:33]=1)([CH3:27])([CH3:26])[CH3:25]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 21874548tert-Butyl {[3-(bromomethyl)phenyl]methyl}carbamateHCID 22050579HCID 22050579, compound

Product 1

HCID 21035387HCID 21035387, compoundYield 20.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 3-bromo-4-(4-fluorobenzyloxy)pyridine-2(1H)-one (from Step 3, synthesis EXAMPLE 59) (0.2 g, 0.67 mmol) in DMF (11 mL) was added K2CO3 (0.26 g, 1.3 mmol) and 3-(bromomethyl)benzylcarbamic acid tert-butyl ester (0.23 g, 0.80 mmol), and the reaction mixture was stirred at 80° C. for 3 hours. The reaction mixture was cooled to room temperature, and concentrated under reduced pressure. The residue was diluted with a 50% aqueous solution of brine (24 mL), and extracted with CHCL3 (4×50 mL). The combined organics was washed water and then brine, dried (MgSO4), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 3:7 EtOAc/hexanes) and recrystallization from MeOH afforded {3-[3-bromo-4-(4-fluorobenzyloxy)-2-oxo-2H-pyridin-1-ylmethyl]benzyl}carbamic acid tert-butyl ester as an off-white solid (0.07 g, 20%): mp 136-138° C.; 1H NMR (300 MHz, CDCl3) δ 7.42-7.37 (m, 2H), 7.30-7.20 (m, 5H), 7.08 (t, J=9 Hz, 2H), 6.04 (d, J=9 Hz, 1H), 5.16 (s, 2H), 5.14 (s, 2H), 4.28 (d, J=6 Hz, 1H), 1.44 (s, 9H). ES HRMS m/z 517.1124 (M+H C25H27BrFN2O4 requires 517.1133).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. additionThe residue was diluted with a 50% aqueous solution of brine (24 mL)
  4. extractionextracted with CHCL3 (4×50 mL)
  5. washThe combined organics was washed water
  6. dry with materialbrine, dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customPurification
  10. customby flash column chromatography (silica, 3:7 EtOAc/hexanes) and recrystallization from MeOH

Sources & evidence

ORD record
ord-877ea1a6d94d4712b098873bb190964d
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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