Sodium Bromide → HCID 59410064, compound

HRID 1915499Notes

Reaction equation

HRID 1915499 reaction equation
[Na+].[Br-:2].CS(O[CH2:8][C@@H:9]1[CH2:13][C:12]([F:15])([F:14])[CH2:11][N:10]1[C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[C:18]([C:25]([F:28])([F:27])[F:26])[CH:17]=1)(=O)=O>C(#N)C.C(OCC)(=O)C.O>[Br:2][CH2:8][C@@H:9]1[CH2:13][C:12]([F:15])([F:14])[CH2:11][N:10]1[C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[C:18]([C:25]([F:28])([F:27])[F:26])[CH:17]=1

Participants

6

Reactant 2

HCID 253881Sodium BromideHCID 59410067HCID 59410067, compound

Product 1

HCID 59410064HCID 59410064, compoundYield 72.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

NaBr (420 mg, 131 μL, 4.08 mmol) was added to a solution of (S)-(4,4-difluoro-1-(4-nitro-3-(trifluoromethyl)phenyl)pyrrolidin-2-yl)methyl methanesulfonate (330 mg, 0.82 mmol) in acetonitrile (2.0 mL) and heated at 80° C. for 16 h. The reaction mixture was diluted with ethyl acetate (10 mL) and water (5 mL). The organic layer was separated, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (15-50% ethyl acetate/hexane) to obtain (S)-2-(bromomethyl)-4,4-difluoro-1-(4-nitro-3-(trifluoromethyl)phenyl)pyrrolidine (230 mg, 72%) as a yellow oil. 1H NMR (400 MHz, DMSO-d6) δ 8.14 (d, J=8.7 Hz, 1H), 7.09-7.07 (m, 2H), 4.76-4.71 (m, 1H), 4.16-3.99 (m, 2H), 3.74 (dd, J=10.6, 3.0 Hz, 1H), 3.60 (t, J=9.7 Hz, 1H), 2.94-2.80 (m, 1H), 2.66-2.55 (m, 1H).

Workup

  1. customThe organic layer was separated
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel column chromatography (15-50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-7766a39ba3d84782ab82ddf9b8e73e2b
Source dataset
uspto-grants-2013_12
Patent number
US08614327B2

Reaction notes

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