Hydrochloric Acid → 1-(4-Amino-3'-fluoro[1,1'-biphenyl]-3-yl)ethanone

HRID 1258074Notes

Reaction equation

HRID 1258074 reaction equation
F[C:2]1C=C(B(O)O)C=CC=1.NC1C=CC(Br)=CC=1C#N.[NH2:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[CH:29]=2)=[CH:24][C:23]=1[C:35]#[N:36].C[Mg]Br.Cl.[C:41](=[O:44])([O-])[O-].[Na+].[Na+]>C1COCC1.C(OCC)(=O)C>[NH2:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[CH:29]=2)=[CH:24][C:23]=1[C:35]#[N:36].[NH2:21][C:22]1[CH:23]=[CH:24][C:25]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[CH:29]=2)=[CH:26][C:27]=1[C:41](=[O:44])[CH3:2]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 4297402-Amino-5-bromobenzonitrileHCID 27339863-Fluorophenylboronic acidHCID 220218944-Amino-3'-fluoro-[1,1'-biphenyl]-3-carbonitrileHCID 178418573HCID 178418573, compound

Product 2

HCID 220218911-(4-Amino-3'-fluoro[1,1'-biphenyl]-3-yl)ethanoneYield 43%HCID 220218944-Amino-3'-fluoro-[1,1'-biphenyl]-3-carbonitrile

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-Amino-3′-fluoro[1,1′-biphenyl]-3-carbonitrile was prepared from 3-fluorophenyl boronic acid and 2-amino-5-bromobenzonitrile according to the procedure of Example 4. A solution of 4-amino-3′-fluoro[1,1′-biphenyl]-3-carbonitrile (6.65 g, 31.3 mmol) in anhydrous THF (100 mL) was treated drop wise at room temperature under nitrogen with methylmagnesium bromide (3.0 M in ether, 21 mL, 63 mmol). The reaction mixture was then heated at gentle reflux for 1.5 hours, cooled to room temperature, and treated with 3N aqueous hydrogen chloride solution (30 mL). The resulted mixture was heated at reflux for 3 hours, cooled to ambient temperature, and adjusted to a pH of 5-6 by the addition of a saturated aqueous sodium carbonate solution. Ethyl acetate (100 mL) was added, the organic layer was separated and the aqueous layer was extracted with ethyl acetate (3×50 mL). The combined organic layers were dried (MgSO4) and evaporated. The residue was purified by a silica gel chromatography (hexane:ethyl acetate/3:1) to afford 1-(4-amino-3′-fluoro[1,1′-biphenyl]-3-yl)ethanone (3.1 g, 43%): mp 156-157° C.

Workup

  1. temperatureThe reaction mixture was then heated
  2. temperatureat gentle reflux for 1.5 hours
  3. temperatureThe resulted mixture was heated
  4. temperatureat reflux for 3 hours
  5. temperaturecooled to ambient temperature
  6. customthe organic layer was separated
  7. extractionthe aqueous layer was extracted with ethyl acetate (3×50 mL)
  8. dry with materialThe combined organic layers were dried (MgSO4)
  9. customevaporated
  10. customThe residue was purified by a silica gel chromatography (hexane:ethyl acetate/3:1)

Sources & evidence

ORD record
ord-0d2e3b82533f4726852fb93c4c395c15
Source dataset
uspto-grants-2013_06
Patent number
US08466146B2

Reaction notes

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