Diethyl Ether → Tert-butyl 2-(3-cyano-4-(2-fluoropyridin-4-yl)phenyl)acetate

HRID 1036281Notes

Reaction equation

HRID 1036281 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:10]2[CH:15]=[CH:14][N:13]=[C:12]([F:16])[CH:11]=2)=[C:6]([CH:9]=1)[C:7]#[N:8].[Cl-].[C:18]([O:22][C:23](=[O:26])[CH2:24][Zn+])([CH3:21])([CH3:20])[CH3:19].CCOCC>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].CC(P(C(C)(C)C)[C-]1C=CC=C1)(C)C.C1C=CC([C-]2C(C3C=CC=CC=3)=C(C3C=CC=CC=3)C(C3C=CC=CC=3)=C2C2C=CC=CC=2)=CC=1.[Fe+2].C1COCC1>[C:7]([C:6]1[CH:9]=[C:2]([CH2:24][C:23]([O:22][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:26])[CH:3]=[CH:4][C:5]=1[C:10]1[CH:15]=[CH:14][N:13]=[C:12]([F:16])[CH:11]=1)#[N:8]

Participants

7

Reactant 3

HCID 3283Diethyl EtherHCID 584476735-Bromo-2-(2-fluoropyridin-4-yl)benzonitrileHCID 178451183HCID 178451183, compound

Product 1

HCID 68247402Tert-butyl 2-(3-cyano-4-(2-fluoropyridin-4-yl)phenyl)acetate

Reagents, catalysts & solvents 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 129828017Ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane;iron(2+);(2,3,4,5-tetraphenylcyclopenta-1,4-dien-1-yl)benzeneCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

To a sealed tube were added 5-bromo-2-(2-fluoropyridin-4-yl)benzonitrile 206-3 (42 mg, 0.16 mmol), 0.5 M (2-tert-butoxy-2-oxoethyl) zinc(II) chloride 86-5 in ether (0.46 mL, 0.23 mmol), Pd(dba)2 (4.4 mg, 0.008 mmol), Q-phos (10.8 mg, 0.015 mmol) and THF (1 mL). The reaction mixture was bubbled with nitrogen for 1 minute and stirred at 100° C. for 1 hour. After cooling to room temperature, all the solvents were evaporated and the residue was redissolved in ethyl acetate, washed with water and brine, dried over Na2SO4 and concentrated to dryness by rotary evaporation. The crude product was purified by silica gel flash chromatography and eluted with 20% ethyl acetate in hexane to give tert-butyl 2-(3-cyano-4-(2-fluoropyridin-4-yl)phenyl)acetate 206-5. MS m/z 313.2 (M+1).

Workup

  1. customThe reaction mixture was bubbled with nitrogen for 1 minute
  2. temperatureAfter cooling to room temperature
  3. customall the solvents were evaporated
  4. dissolutionthe residue was redissolved in ethyl acetate
  5. washwashed with water and brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to dryness by rotary evaporation
  8. customThe crude product was purified by silica gel flash chromatography
  9. washeluted with 20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-c564aa7089e84e86b010144a34b108f8
Source dataset
uspto-grants-2013_10
Patent number
US08546396B2

Reaction notes

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