Methyl Acrylate → HCID 67492674, compound

HRID 1922388Notes

Reaction equation

HRID 1922388 reaction equation
I[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][CH:9]1[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]1.[C:16]([O:20][CH3:21])(=[O:19])[CH:17]=[CH2:18].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(C(C)C)CC)(C)C>CN(C=O)C.CO.C(Cl)Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:15][N:12]1[CH2:13][CH2:14][CH:9]([NH:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2/[CH:18]=[CH:17]/[C:16]([O:20][CH3:21])=[O:19])[CH2:10][CH2:11]1

Participants

8

Reactant 4

HCID 7294Methyl AcrylateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 28978254HCID 28978254, compound

Product 1

HCID 67492674HCID 67492674, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
100 °C

Procedure

A solution of N-(2-iodophenyl)-1-methylpiperidin-4-amine (550 mg, 1.74 mmol), methyl acrylate (157 μL, 1.74 mmol), palladium acetate (39 mg, 0.17 mmol), tri-o-tolylphosphine (106 mg, 0.35) and diisopropylethylamine (608 μL, 3.48 mmol) in 7 mL DMF was deoxygenated with argon then heated at 100° C. for 5 hours. The mixture was cooled to room temperature then partitioned between EtOAc (150 mL) and H2O (20 mL). After extraction, the organic layer was separated and rinsed with brine. The organic layer was dried over Na2SO4, filtered and concentrated to give a yellow residue, which was subjected to flash chromatography on silica gel using 5%, 2M NH3 in MeOH/CH2Cl2. A viscous yellow oil was obtained (350 mg, 73.4%). 1H-NMR (CDCl3) δ 7.85 (d, J=15.9 Hz, 1H), 7.37-7.35 (m, 1H), 7.24-7.21 (m, 1H), 6.72-6.67 (m, 2H), 6.33 (d, J=15.9 Hz, 1H), 3.88-3.85 (m, 1H), 3.81 (s, 3H), 3.36 (brs, 1H), 2.84-2.81 (m, 2H), 2.31 (s, 3H), 2.18-2.05 (m, 4H), 1.63-1.51 (m, 2H). MS (ESI): 275.2 (M+1, 100%).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. customthen partitioned between EtOAc (150 mL) and H2O (20 mL)
  3. extractionAfter extraction
  4. customthe organic layer was separated
  5. washrinsed with brine
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a yellow residue, which
  10. customA viscous yellow oil was obtained (350 mg, 73.4%)

Sources & evidence

ORD record
ord-fd35a092ff3b42608d26ce25843ae43e
Source dataset
uspto-grants-2012_05
Patent number
US08173813B2

Reaction notes

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