Diethyl Ether → Tert-butyl 2-(6-chloro-5-fluoropyridin-3-yl)acetate

HRID 1036252Notes

Reaction equation

HRID 1036252 reaction equation
Br[C:2]1[CH:3]=[C:4]([F:9])[C:5]([Cl:8])=[N:6][CH:7]=1.[Cl-].[C:11]([O:15][C:16](=[O:19])[CH2:17][Zn+])([CH3:14])([CH3:13])[CH3:12].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>[Cl:8][C:5]1[N:6]=[CH:7][C:2]([CH2:17][C:16]([O:15][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:19])=[CH:3][C:4]=1[F:9]

Participants

7

Reactant 3

HCID 3283Diethyl EtherHCID 27632855-Bromo-2-chloro-3-fluoropyridineHCID 178451183HCID 178451183, compound

Product 1

HCID 58365072Tert-butyl 2-(6-chloro-5-fluoropyridin-3-yl)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-chloro-3-fluoropyridine 190-1 (210 mg, 1.0 mmol), 0.5 M (2-tert-butoxy-2-oxoethyl) zinc(II) chloride 86-5 in ether (2.4 mL, 1.2 mmol), Pd(dba)2 (29 mg, 0.005 mmol), Q-phos (71 mg, 0.10 mmol) and THF (3 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-(6-chloro-5-fluoropyridin-3-yl)acetate 190-3. MS m/z 246.1 (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-4ca27f869f214fa4b13a34e617d160b5
Source dataset
uspto-grants-2013_10
Patent number
US08546396B2

Reaction notes

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