Hydrochloric Acid → Ethyl 2-[(2'-cyano-3-fluorobiphenyl-4-yl)methyl]-3-oxohexanoate

HRID 1688867Notes

Reaction equation

HRID 1688867 reaction equation
[H-].[Na+].[O:3]=[C:4]([CH2:11][CH2:12][CH3:13])[CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7].Br[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[C:23]([C:28]#[N:29])=[CH:24][CH:25]=[CH:26][CH:27]=2)=[CH:18][C:17]=1[F:30].Cl>O1CCCC1.C1(C(F)(F)F)C=CC=CC=1>[C:28]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[C:19]1[CH:20]=[CH:21][C:16]([CH2:15][CH:5]([C:4](=[O:3])[CH2:11][CH2:12][CH3:13])[C:6]([O:8][CH2:9][CH3:10])=[O:7])=[C:17]([F:30])[CH:18]=1)#[N:29]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 238498Ethyl 3-oxohexanoateHCID 574600744'-(Bromomethyl)-3'-fluorobiphenyl-2-carbonitrile

Product 1

HCID 57460949Ethyl 2-[(2'-cyano-3-fluorobiphenyl-4-yl)methyl]-3-oxohexanoateYield 76%

Reagents, catalysts & solvents 2

HCID 7368(Trifluoromethyl)benzeneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of 3′-fluoro-4′-methylbiphenyl-2-carbonitrile (110 g), N-bromosuccinimide (97.3 g) and benzotrifluoride (1.0 L) was added azobisisobutyronitrile (1.71 g), and the mixture was heated to an internal temperature of 78° C. and stirred for 16 hr. The reaction mixture was cooled to around 40° C., and the insoluble material was removed to give a solution of 4′-(bromomethyl)-3′-fluorobiphenyl-2-carbonitrile in benzotrifluoride. To a suspension of sodium hydride (60% in oil, 25 g) in tetrahydrofuran (750 mL) was added dropwise a solution of ethyl 3-oxohexanoate (164 g) in tetrahydrofuran (250 mL) at 0° C. The reaction mixture was stirred at room temperature for 1 hr, and a solution of 4′-(bromomethyl)-3′-fluorobiphenyl-2-carbonitrile in benzotrifluoride above mentioned was added at 0° C. The reaction mixture was further stirred at room temperature for 16 hr, and added to 1 M hydrochloric acid (1.0 L), and the obtained mixture was concentrated under reduced pressure. The obtained mixture was extracted with ethyl acetate, and the obtained extract was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was purified by silica gel column chromatography to give the title compound as a colorless oil (145 g, 76%).

Workup

  1. stirringThe reaction mixture was further stirred at room temperature for 16 hr
  2. concentrationthe obtained mixture was concentrated under reduced pressure
  3. extractionThe obtained mixture was extracted with ethyl acetate
  4. extractionthe obtained extract
  5. washwas washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. customthe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-89b86a4b70794c8fa458ad02571f7738
Source dataset
uspto-grants-2012_04
Patent number
US08148383B2

Reaction notes

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