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

HRID 1036276Notes

Reaction equation

HRID 1036276 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].C1([C-]2C(C3C=CC=CC=3)=C(C3C=CC=CC=3)C(C3C=CC=CC=3)=C2C2C=CC=CC=2)C=CC=CC=1.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[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
70 °C

Procedure

In a sealed tube, a mixture of 5-bromo-2-chloro-3-fluoropyridine 205-1 (631 mg, 3 mmol), 0.5 M (2-tert-butoxy-2-oxoethyl) zinc(II) chloride 205-2 in ether (6.6 mL, 3.3 mmol), Pd(dba)2 (87 mg, 0.15 mmol), 1,2,3,4,5-pentaphenyl-1′-(di-t-butylphosphino)ferrocene (Q-phos, 107 mg, 0.15 mmol), and THF (12 mL) under argon was stirred at 70° C. for 18 hours. After cooled to room temperature, 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, eluted with 30% ethyl acetate in hexane to give tert-butyl 2-(6-chloro-5-fluoropyridin-3-yl)acetate 205-3 as a brown oil. MS m/z 246.1 (M+1).

Workup

  1. temperatureAfter cooled to room temperature
  2. customthe solvents were evaporated
  3. dissolutionthe residue was redissolved in ethyl acetate
  4. washwashed with water and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to dryness by rotary evaporation
  7. customThe crude product was purified by silica gel flash chromatography
  8. washeluted with 30% ethyl acetate in hexane

Sources & evidence

ORD record
ord-e7816d1529d0422babaa825b34cb5707
Source dataset
uspto-grants-2013_10
Patent number
US08546396B2

Reaction notes

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