Methyl Acrylate → Methyl (2E)-3-(3-{1-[(tert-butoxycarbonyl)amino]ethyl}-5-chloro-2-methoxy-6-methylphenyl)acrylate

HRID 511015Notes

Reaction equation

HRID 511015 reaction equation
Br[C:2]1[C:3]([O:20][CH3:21])=[C:4]([CH:10]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH3:11])[CH:5]=[C:6]([Cl:9])[C:7]=1[CH3:8].[C:22]([O:26][CH3:27])(=[O:25])[CH:23]=[CH2:24].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:15]([O:14][C:13]([NH:12][CH:10]([C:4]1[C:3]([O:20][CH3:21])=[C:2](/[CH:24]=[CH:23]/[C:22]([O:26][CH3:27])=[O:25])[C:7]([CH3:8])=[C:6]([Cl:9])[CH:5]=1)[CH3:11])=[O:19])([CH3:18])([CH3:17])[CH3:16]

Participants

7

Reactant 4

HCID 7294Methyl AcrylateHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 88543336Tert-butyl[1-(3-bromo-5-chloro-2-methoxy-4-methylphenyl)ethyl]carbamate

Product 1

HCID 86666936Methyl (2E)-3-(3-{1-[(tert-butoxycarbonyl)amino]ethyl}-5-chloro-2-methoxy-6-methylphenyl)acrylateYield 68.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

Into a sealed tube was placed a suspension of tert-butyl[1-(3-bromo-5-chloro-2-methoxy-4-methylphenyl)ethyl]carbamate [from Example 113, step 1, peak 2] (1.0 g, 2.6 mmol) in DMF (15 mL) that was degassed with nitrogen and treated with methyl acrylate (0.83 mL, 9.2 mmol), triphenylphosphine (97 mg, 0.37 mmol), and palladium acetate (59 mg, 0.26 mmol). Lastly, triethylamine (1.1 mL, 7.9 mmol) was added and the reaction mixture was heated at 130° C. for 16 hours. After cooling to room temperature, the mixture was filtered over Celite and the Celite was washed with EtOAc (100 mL). The EtOAc was washed with water, brine, dried over anhydrous sodium sulfate, filtered, and concentrated to a crude foam. The crude material was dissolved in 2:1 hexane/dichloromethane and purified by flash column chromatography using EtOAc in hexanes (0%-30% over 30 min) to give the desired product (0.68 g, 68%) as a white foam. LCMS for C14H16ClO3 (M−NHBoc)+: m/z=267.1. Found: 266.9.

Workup

  1. customInto a sealed tube was placed
  2. customwas degassed with nitrogen
  3. temperatureAfter cooling to room temperature
  4. filtrationthe mixture was filtered over Celite
  5. washthe Celite was washed with EtOAc (100 mL)
  6. washThe EtOAc was washed with water, brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated to a crude foam
  10. dissolutionThe crude material was dissolved in 2:1 hexane/dichloromethane
  11. custompurified by flash column chromatography
  12. customEtOAc in hexanes (0%-30% over 30 min)

Sources & evidence

ORD record
ord-597d8f1c75684c2989b84982c1f61dbc
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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