HCID 22049994, compound → HCID 22050368, compound

HRID 1867107Notes

Reaction equation

HRID 1867107 reaction equation
[Br:1][C:2]1[C:7](=[O:8])[N:6]([C:9]2[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=2[F:16])[C:5]([CH3:17])=[C:4]([CH:18]=[O:19])[C:3]=1[O:20][CH2:21][C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=1[F:29]>CO>[Br:1][C:2]1[C:7](=[O:8])[N:6]([C:9]2[C:10]([F:16])=[CH:11][CH:12]=[CH:13][C:14]=2[F:15])[C:5]([CH3:17])=[C:4]([CH2:18][OH:19])[C:3]=1[O:20][CH2:21][C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=1[F:29]

Participants

3

Reactant 1

HCID 22049994HCID 22049994, compound

Product 1

HCID 22050368HCID 22050368, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a −20° C. solution of 5-bromo-4-[(2,4-difluorobenzyl)oxy]-1-(2,6-difluorophenyl)-2-methyl-6-oxo-1,6-dihydropyridine-3-carbaldehyde (0.659 g, 1.40 mmol) in methanol (10 mL) was added, portionwise, solid sodium borohyride (3.6 g, 96 mmol) over one hour until complete consumption of starting material by LCMS analysis. Next, the reaction mixture was diluted with 500 mL of ethyl acetate and washed with 3×200 mL of water. The resulting organic extract was Na2SO4 dried, filtered, and concentrated in vacuo to approximately 100 mL volume. The resulting liquid was diluted with hexanes (100 mL) to furnish an amorphous solid that was collected and dried at 1 mm Hg vacuum to furnish (620 mg, 94%) of the desired product. 1H NMR (400 MHz, d4-MeOH) δ 7.70 (app q, J=8.3 Hz, 1H), 7.62 (app tt, J=10.4, 6.3 Hz, 1H), 7.25 (app t, J=8.6 Hz, 2H), 7.03 (app t, J=8.6 Hz, 1H), 6.88 (app t, J=8.5 Hz, 1H), 5.31 (s, 2H), 4.58 (s, 2H), 2.17 (s, 3H); LC/MS C-18 column, tr=2.49 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50° C.). ES-MS m/z 472 (M+H). ES-HRMS m/z 472.0152 (M+H calcd for C20H15BrF4NO3 requires 472.0166).

Workup

  1. customportionwise, solid sodium borohyride (3.6 g, 96 mmol) over one hour until complete consumption of starting material by LCMS analysis
  2. additionNext, the reaction mixture was diluted with 500 mL of ethyl acetate
  3. washwashed with 3×200 mL of water
  4. extractionThe resulting organic extract
  5. customdried
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo to approximately 100 mL volume
  8. additionThe resulting liquid was diluted with hexanes (100 mL)
  9. customto furnish an amorphous solid
  10. customthat was collected
  11. customdried at 1 mm Hg vacuum

Sources & evidence

ORD record
ord-2871461c41594071b92af36f2847c778
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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