tert-Butyl acrylate → Tert-butyl 3-(6-aminopyridin-3-yl)prop-2-enoate

HRID 2172021Notes

Reaction equation

HRID 2172021 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5](Br)=[CH:4][N:3]=1.CCN(C(C)C)C(C)C.[C:18]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])(=[O:21])[CH:19]=[CH2:20].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>CN(C=O)C.C(#N)CC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:1][C:2]1[N:3]=[CH:4][C:5](/[CH:20]=[CH:19]/[C:18]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 15458tert-Butyl acrylateHCID 706222-Amino-5-bromopyridineHCID 80271Tri-o-tolylphosphineHCID 81531Diisopropylethylamine

Product 1

HCID 57777730Tert-butyl 3-(6-aminopyridin-3-yl)prop-2-enoateYield 99.7%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 7854PropionitrileSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-amino-5-bromopyridine (300 mg, 1.73 mmol) in DMF (1.5 mL) and proprionitrile (3.5 mL) under Argon were added DIPEA (613 μL, 3.71 mmol), tert-butyl acrylate (1.02 mL, 7.06 mmol), tri(o-tolyl)phosphine (106 mg, 0.35 mmol) and palladium acetate (39 mg, 0.17 mmol). The mixture was stirred at 100° C. for 20 h, then allowed to come back to room temperature, filtered through Celite pad and rinsed with EtOAc. The residue obtained after concentration was purified by flash chromatography (eluent: 95/5 DCM/MeOH) to give the title compound as an orange solid (380 mg, quantitative).

Workup

  1. customto come back to room temperature
  2. filtrationfiltered through Celite pad
  3. washrinsed with EtOAc
  4. customThe residue obtained
  5. concentrationafter concentration
  6. customwas purified by flash chromatography (eluent: 95/5 DCM/MeOH)

Sources & evidence

ORD record
ord-01a3cf67764d48b69c1d9749d89b68f4
Source dataset
uspto-grants-2015_06
Patent number
US09051321B2

Reaction notes

Loading…