Bromide ion → HCID 9977053, compound

HRID 2256404Notes

Reaction equation

HRID 2256404 reaction equation
[C:1]([NH:11][C:12]1[CH:17]=[C:16]([F:18])[C:15]([C:19]2[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=2)=[C:14]([F:25])[CH:13]=1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].[H-].[Na+].[Br-].[CH2:29]1[CH2:33]OC[CH2:30]1>>[CH2:33]([N:11]([C:1]([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2])[C:12]1[CH:13]=[C:14]([F:25])[C:15]([C:19]2[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=2)=[C:16]([F:18])[CH:17]=1)[CH:29]=[CH2:30]

Participants

5

Reactant 4

HCID 259Bromide ionHCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 10427343HCID 10427343, compound

Product 1

HCID 9977053HCID 9977053, compound

Procedure

A mixture of N-carbobenzyloxy-4-(3-pyridyl)-3,5-difluoroaniline (PREPARATION 3, 543 mg, 1.60 mmol) in anhydrous THF (40 ml) is treated with sodium hydride (60% dispersion in mineral oil, 128 mg, 3.19 mmol, 2 eq). The reaction is kept under an atmosphere of nitrogen at 20°-25° for 0.5 hr. After this time, ally bromide (691 μl, 7.99 mmol, 5 eq) is added. Stirring is continued at 20°-25° for 16 hr. After this time, the reaction is carefully quenched with water (20 ml). The layers are separated and the aqueous layer is extracted with ethyl acetate (3×25 ml). The combined organics phases are washed with brine, dried (sodium sulfate), filtered and concentrated under reduced pressure. The concentrate is purified by silica gel chromatography (125 g of silica gel) eluting with acetonitrile/chloroform (3/97-1 l). The appropriate fractions are concentrated to give the title compound. An analytical sample is prepared by preparative TLC (SG, acetonitrile/chloroform-6/94), mp=92°-93°; FTIR (mull) cm-1 3068, 3061, 1710, 1705, 1643, 1635, 1412, 1263, 1024, 733; MS (EI) m/z: 380, 336, 309, 245, 91, 65; NMR (CDCl3) 8.72, 8.62, 7.99, 7.42-7.36, 7.03, 5.94, 5.23-5.18 and 4.34 δ.

Workup

  1. waitis continued at 20°-25° for 16 hr
  2. customAfter this time, the reaction is carefully quenched with water (20 ml)
  3. customThe layers are separated
  4. extractionthe aqueous layer is extracted with ethyl acetate (3×25 ml)
  5. washThe combined organics phases are washed with brine
  6. dry with materialdried (sodium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe concentrate is purified by silica gel chromatography (125 g of silica gel)
  10. washeluting with acetonitrile/chloroform (3/97-1 l)
  11. concentrationThe appropriate fractions are concentrated

Sources & evidence

ORD record
ord-3f9ec8d180c547d3bca70e8f1a298eb9
Source dataset
uspto-grants-1997_08
Patent number
US05654435

Reaction notes

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