Triethylamine → HCID 131732502, compound

HRID 1854556Notes

Reaction equation

HRID 1854556 reaction equation
C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[C:23]([O:27][CH2:28][CH3:29])(=[O:26])[CH:24]=[CH2:25].Br[C:31]1[CH:40]=[CH:39][CH:38]=[C:37]2[C:32]=1[CH2:33][C@H:34]([CH2:53][O:54][Si:55]([C:58]([CH3:61])([CH3:60])[CH3:59])([CH3:57])[CH3:56])[N:35]([C:42](=[O:52])[CH2:43][C:44]1[C:49]([Cl:50])=[CH:48][CH:47]=[CH:46][C:45]=1[Cl:51])[C@H:36]2[CH3:41].C(N(CC)CC)C>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(#N)C>[Si:55]([O:54][CH2:53][C@H:34]1[CH2:33][C:32]2[C:37](=[CH:38][CH:39]=[CH:40][C:31]=2/[CH:25]=[CH:24]/[C:23]([O:27][CH2:28][CH3:29])=[O:26])[C@H:36]([CH3:41])[N:35]1[C:42](=[O:52])[CH2:43][C:44]1[C:49]([Cl:50])=[CH:48][CH:47]=[CH:46][C:45]=1[Cl:51])([C:58]([CH3:61])([CH3:59])[CH3:60])([CH3:57])[CH3:56]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 8821Ethyl AcrylateHCID 80271Tri-o-tolylphosphineHCID 123166480HCID 123166480, compound2×

Product 1

HCID 131732502HCID 131732502, compoundYield 96.9%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
160 °C

Procedure

Bubble nitrogen through acetonitrile. Place tri-o-tolylphosphine (72.3 mg, 0.23 mmol), palladium (II) acetate (11.8 mg, 0.052 mmol) and acetonitrile (0.96 mL) in a microwave vessel. Stir 10 min. Add ethyl acrylate (0.31 mL, 2.88 mmol). Add 1-[(1S,3R)-5-bromo-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl]-2-(2,6-dichlorophenyl)ethanone (0.54 g, 0.96 mmol). Add triethylamine (0.40 mL, 2.88 mmol) and stir vigorously. Blow nitrogen across the surface of the reaction. Seal the vessel and heat to 160° C. for 35 min in a microwave. Cool to room temperature and dilute with ethyl acetate. Filter the precipitate and wash with ethyl acetate. Concentrate the filtrate under reduced pressure to give a brown oil. Combine with the crude product from a substantially same reaction run with 0.27 mmol of 1-[(1S,3R)-5-bromo-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl]-2-(2,6-dichlorophenyl)ethanone. Purify the combined residues by silica gel chromatography, eluting with ethyl acetate: hexanes (gradient, 0-10%) to give the title compound (0.54 g, 0.93 mmol). MS (m/z): 576 (M+1). The following compound is prepared essentially by the method of Preparation 14.

Workup

  1. customBubble nitrogen through acetonitrile
  2. customBlow nitrogen across the surface of the reaction
  3. customSeal the vessel
  4. temperatureCool to room temperature
  5. filtrationFilter the precipitate
  6. washwash with ethyl acetate
  7. concentrationConcentrate the filtrate under reduced pressure
  8. customto give a brown oil
  9. customPurify the combined residues by silica gel chromatography
  10. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-86330da8c1cf42319759b836600f86a2
Source dataset
uspto-grants-2015_02
Patent number
US08962654B2

Reaction notes

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