Sodium Carbonate → HCID 123662034, compound

HRID 1854567Notes

Reaction equation

HRID 1854567 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][C@H:5]([CH2:24][O:25][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27])[N:6]([C:13](=[O:23])[CH2:14][C:15]1[C:20]([Cl:21])=[CH:19][CH:18]=[CH:17][C:16]=1[Cl:22])[C@H:7]2[CH3:12].[CH2:33](OB(C=C)OCCCC)[CH2:34]CC.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Si:26]([O:25][CH2:24][C@H:5]1[CH2:4][C:3]2[C:8](=[CH:9][CH:10]=[CH:11][C:2]=2[CH:33]=[CH2:34])[C@H:7]([CH3:12])[N:6]1[C:13](=[O:23])[CH2:14][C:15]1[C:20]([Cl:21])=[CH:19][CH:18]=[CH:17][C:16]=1[Cl:22])([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 236543Dibutyl Vinylboronate (stabilized with Phenothiazine)HCID 123166480HCID 123166480, compound

Product 1

HCID 123662034HCID 123662034, compoundYield 81.5%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Dissolve 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 (300 mg, 0.54 mmol) and vinylboronic acid dibutyl ester (0.24 mL, 1.08 mmol) in 1,4-dioxane (5.4 mL). Add aqueous Na2CO3 solution (2.7 mL, 2M in water). Degas with nitrogen 10 min Add bis(triphenylphosphine)palladium(II) chloride (76 mg, 0.11 mmol). Heat to 80° C. Stir 2 hours. Add water and extract with ethyl acetate three times. Combine the ethyl acetate extracts, dry over sodium sulfate, filter, and concentrate under reduced pressure to give a residue. Purify the residue by silica gel chromatography, eluting with ethyl acetate:hexanes (gradient, 5-80%) to give the title compound as a white foam (220 mg, 0.44 mmol). MS (m/z): 504 (M+1).

Workup

  1. customDegas with nitrogen 10 min
  2. extractionAdd water and extract with ethyl acetate three times
  3. dry with materialdry over sodium sulfate
  4. filtrationfilter
  5. concentrationconcentrate under reduced pressure
  6. customto give a residue
  7. customPurify the residue by silica gel chromatography
  8. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-57260f38cc52432e9061699e6b626f0e
Source dataset
uspto-grants-2015_02
Patent number
US08962654B2

Reaction notes

Loading…