N-bromobutanimide → HCID 22050160, compound

HRID 1832066Notes

Reaction equation

HRID 1832066 reaction equation
[F:1][C:2]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:3]=1[CH2:4][O:5][C:6]1[CH:11]=[C:10]([CH3:12])[N:9]([C:13]2[CH:14]=[C:15]([CH:20]=[CH:21][C:22]=2[F:23])[C:16]([O:18][CH3:19])=[O:17])[C:8](=[O:24])[CH:7]=1.[Br:30]N1C(=O)CCC1=O.C([O-])(O)=O.[Na+]>>[Br:30][C:7]1[C:8](=[O:24])[N:9]([C:13]2[CH:14]=[C:15]([CH:20]=[CH:21][C:22]=2[F:23])[C:16]([O:18][CH3:19])=[O:17])[C:10]([CH3:12])=[CH:11][C:6]=1[O:5][CH2:4][C:3]1[CH:25]=[CH:26][C:27]([F:29])=[CH:28][C:2]=1[F:1]

Participants

4

Reactant 3

HCID 67184N-bromobutanimideHCID 516892Sodium BicarbonateHCID 22050189HCID 22050189, compound

Product 1

HCID 22050160HCID 22050160, compoundYield 40.2%

Procedure

A 100 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with methyl 3-[4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-4-fluorobenzoate (7.3 g, 18 mmol) and N-methyl-2-pyrrolidine (20 mL). N-Bromo succinimide (3.5 g, 19.8 mmol) was added and the reaction mixture was stirred at room temperature for 30 minutes. The mixture poured into saturated aqueous NaHCO3 and extracted with ethyl acetate. The organic layer was washed with brine, dried with Na2SO4, and concentrated in vacuo. The residue was triturated with diethyl ether and filtered to give the title compound as a white powder (3.49 g). 1H NMR (400 MHz, CD3OD) δ 8.16 (qd, J=3, 6.8 and 15.6 Hz, 1H), 7.84 (d, J=2.12 Hz, 1H), 7.64 (q, J=8.4 and 14.8 Hz, 1H), 7.29 (d, J=8.4 Hz, 1H), 7.04 (m, 2H), 6.60 (s, 1H), 5.34 (s, 2H), 3.87 (s, 3H), 2.00 (s, 3H) ppm. 19F NMR (400 MHz, CD3OD) δ−111.51 (1 F), −115.98 (1 F), −117.43 (1 F) ppm. ES-HRMS m/z 494.0387(M+H calcd for C22H19BrF2NO5 requires 494.0409). Step 2 Preparation of 3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-4-fluorobenzoic acid

Workup

  1. customA 100 mL round bottomed flask equipped with stirbar and nitrogen inlet
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried with Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was triturated with diethyl ether
  7. filtrationfiltered

Sources & evidence

ORD record
ord-a3fa9aa71edd4f089a87360ae4125d3f
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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