Diethyl Ether → Tert-butyl 2-(2-(2-methylpyridin-4-yl)pyrimidin-5-yl)acetate

HRID 592200Notes

Reaction equation

HRID 592200 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([CH3:14])[CH:9]=2)=[N:6][CH:7]=1.[Cl-].[C:16]([O:20][C:21](=[O:24])[CH2:22][Zn+])([CH3:19])([CH3:18])[CH3:17].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>[CH3:14][C:10]1[CH:9]=[C:8]([C:5]2[N:4]=[CH:3][C:2]([CH2:22][C:21]([O:20][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:24])=[CH:7][N:6]=2)[CH:13]=[CH:12][N:11]=1

Participants

7

Reactant 3

HCID 3283Diethyl EtherHCID 584476465-Bromo-2-(2-methylpyridin-4-yl)pyrimidineHCID 178451183HCID 178451183, compound

Product 1

HCID 58447797Tert-butyl 2-(2-(2-methylpyridin-4-yl)pyrimidin-5-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-(2-methylpyridin-4-yl)pyrimidine 183-3 (50 mg, 0.20 mmol), 0.5 M (2-tert-butoxy-2-oxoethyl) zinc(II) chloride in ether (0.60 mL, 0.30 mmol), Pd(dba)2 (6 mg, 0.01 mmol), Q-phos (14 mg, 0.02 mmol) and THF (1.5 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 25% ethyl acetate in hexane to give tert-butyl 2-(2-(2-methylpyridin-4-yl)pyrimidin-5-yl)acetate 183-4. MS m/z 286.2 (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 25% ethyl acetate in hexane

Sources & evidence

ORD record
ord-aa50bf68056a4203b014a70259ec8e5f
Source dataset
uspto-grants-2016_01
Patent number
US09238646B2

Reaction notes

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