Sodium Hydroxide → 5-(5-Bromothiazol-2-yl)-2-fluorobenzonitrile

HRID 1891447Notes

Reaction equation

HRID 1891447 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:7]([C:10]2[S:11][CH:12]=[CH:13][N:14]=2)=[CH:6][C:3]=1[C:4]#[N:5].[Br:15]N1C(=O)CCC1=O.[OH-].[Na+]>CN(C=O)C>[Br:15][C:12]1[S:11][C:10]([C:7]2[CH:8]=[CH:9][C:2]([F:1])=[C:3]([CH:6]=2)[C:4]#[N:5])=[N:14][CH:13]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 67184N-bromobutanimideHCID 583671252-Fluoro-5-(thiazol-2-yl)benzonitrile

Product 1

HCID 583671525-(5-Bromothiazol-2-yl)-2-fluorobenzonitrileYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 2-fluoro-5-(thiazol-2-yl)benzonitrile (21.8 g, 106.7 mmol) in anhydrous DMF (200 mL) was added recrystallized N-bromosuccinimide (22.7 g, 128 mmol). The reaction mixture was stirred at room temperature for 23 h under N2. The reaction mixture was basified with 1N NaOH and washed with EA and brine. The combined organic layers were dried over MgSO4, filtered, and concentrated to yield orange oil. The crude product was purified by silica gel flash chromatography (20% EA/Hexanes) to produce 21 mg (70%) of 5-(5-bromothiazol-2-yl)-2-fluorobenzonitrile THZ INT-2 as half-white solid. LCMS-ESI (m/z) calculated for C10H4BrFN2S: 283.1; found 284.9 [M+H]+, tR=3.82 min. 1H NMR (400 MHz, CDCl3) δ 8.15 (dd, J=5.9, 2.3 Hz, 1H), 8.08 (ddd, J=8.8, 4.9, 2.3 Hz, 1H), 7.78 (d, J=4.8 Hz, 1H), 7.31 (t, J=8.6 Hz, 1H).

Workup

  1. washwashed with EA and brine
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto yield orange oil
  6. customThe crude product was purified by silica gel flash chromatography (20% EA/Hexanes)

Sources & evidence

ORD record
ord-573921631afe4d93a92db5bba325f8a9
Source dataset
uspto-grants-2013_08
Patent number
US08507538B2

Reaction notes

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