Dichloromethane → Tert-butyl (5-(prop-1-en-2-yl)pyridin-3-yl)methylcarbamate

HRID 2070966Notes

Reaction equation

HRID 2070966 reaction equation
[CH2:1](Cl)Cl.Br[C:5]1[CH:6]=[C:7]([CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH:8]=[N:9][CH:10]=1.C(N([CH2:25][CH3:26])CC)C>C(O)(C)C.O.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:1]=[C:25]([C:5]1[CH:6]=[C:7]([CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH:8]=[N:9][CH:10]=1)[CH3:26]

Participants

7

Reactant 3

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 467392903-(N-BOC-aminomethyl)-5-bromopyridine

Product 1

HCID 86647417Tert-butyl (5-(prop-1-en-2-yl)pyridin-3-yl)methylcarbamateYield 85%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 21889133Propan-2-ol--water (1/1)Solvent

Procedure

A solution of potassium isopropenyl trifluoroborate (464 mg, 3.13 mmol), PdCl2(dppf).CH2Cl2 (153 mg, 0.06 mmol), tert-butyl (5-bromopyridin-3-yl)methylcarbamate (900 mg, 3.13 mmol) and triethylamine (475 mg, 4.69 mmol) in i-PrOH—H2O (2:1, 30 mL) was heated under reflux in a nitrogen atmosphere. The reaction mixture was heated at reflux for 4 h, then cooled to rt and diluted with water (40 mL) followed by extraction with diethylether. The organic layers were combined and washed with brine, dried over sodium sulfate and then filtered. The solvent was removed under vacuum, and the crude product was purified by silica gel chromatography (eluting with 45% EtOAc/hexanes) to afford tert-butyl (5-(prop-1-en-2-yl)pyridin-3-yl)methylcarbamate as a white solid in 85% yield. (5-(prop-1-en-2-yl)pyridin-3-yl)methanamine was then generated by removal of the Boc protecting group by treatment with HCl (in methanol or dioxane) or trifluoroacetic acid in dichloromethane.

Workup

  1. temperatureunder reflux in a nitrogen atmosphere
  2. temperatureThe reaction mixture was heated
  3. temperatureat reflux for 4 h
  4. extractionfollowed by extraction with diethylether
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customThe solvent was removed under vacuum
  9. customthe crude product was purified by silica gel chromatography (eluting with 45% EtOAc/hexanes)

Sources & evidence

ORD record
ord-ef7f6c239bb9468285edd60896d534dc
Source dataset
uspto-grants-2012_10
Patent number
US08299267B2

Reaction notes

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