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

HRID 1036284Notes

Reaction equation

HRID 1036284 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([F:14])[CH:9]=2)=[C:4]([F:15])[CH:3]=1.[Cl-].[C:17]([O:21][C:22](=[O:25])[CH2:23][Zn+])([CH3:20])([CH3:19])[CH3:18].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>[F:15][C:4]1[CH:3]=[C:2]([CH2:23][C:22]([O:21][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:25])[CH:7]=[CH:6][C:5]=1[C:8]1[CH:13]=[CH:12][N:11]=[C:10]([F:14])[CH:9]=1

Participants

7

Reactant 3

HCID 3283Diethyl EtherHCID 584477994-(4-Bromo-2-fluorophenyl)-2-fluoropyridineHCID 178451183HCID 178451183, compound

Product 1

HCID 58447777Tert-butyl 2-(3-fluoro-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 4-(4-bromo-2-fluorophenyl)-2-fluoropyridine 207-3 (210 mg, 0.76 mmol), 0.5 M (2-tert-butoxy-2-oxoethyl) zinc(II) chloride 86-5 in ether (2.3 mL, 1.14 mmol), Pd(dba)2 (22 mg, 0.04 mmol), Q-phos (54 mg, 0.07 mmol) and THF (5 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-fluoro-4-(2-fluoropyridin-4-yl)phenyl)acetate 207-5. MS m/z 306.2 (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-e6b90edc62224700832fe0e6dba4e224
Source dataset
uspto-grants-2013_10
Patent number
US08546396B2

Reaction notes

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