Potassium Phosphate, Tribasic → 1-((1S,3R)-3-(((tert-butyldimethylsilyl)oxy)methyl)-1-methyl-1,2,3,4-tetrahydroisoquinolin-5-yl)propan-2-one

HRID 1854576Notes

Reaction equation

HRID 1854576 reaction equation
Cl.Br[C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH2:5][C@H:6]([CH2:14][O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[NH:7][C@H:8]2[CH3:13].P([O-])([O-])([O-])=[O:24].[K+].[K+].[K+].[CH3:31][CH2:32][CH2:33]CP(C12CC3CC(CC(C3)C1)C2)C12CC3CC(CC(C3)C1)C2>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC(C)=O>[Si:16]([O:15][CH2:14][C@H:6]1[CH2:5][C:4]2[C:9](=[CH:10][CH:11]=[CH:12][C:3]=2[CH2:31][C:32](=[O:24])[CH3:33])[C@H:8]([CH3:13])[NH:7]1)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneHCID 122412747(1S,3R)-5-Bromo-3-[[(tert-butyldimethylsilyl)oxy]methyl]-1-methyl-1,2,3,4-tetrahydroisoquinoline hydrochloride

Product 1

HCID 1232604161-((1S,3R)-3-(((tert-butyldimethylsilyl)oxy)methyl)-1-methyl-1,2,3,4-tetrahydroisoquinolin-5-yl)propan-2-one

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 180AcetoneSolvent

Conditions

Temperature
70 °C

Procedure

Mix (1S,3R)-5-bromo-3-(((tert-butyldimethylsilyl)oxy)methyl)-1-methyl-1,2,3,4-tetrahydroisoquinoline hydrochloride (2.5 g, 6.14 mmol), acetone (30 mL), potassium phosphate, Tribasic, N-hydrate (3.99 g, 18.4 mmol), CataCXium A (di(1-adamantyl)-n-butylphosphine, 220 mg, 0.61 mmol) and tris(dibenzylideneacetone)dipalladium(0) (290 mg, 0.31 mmol). Stir 2 days at 70° C. Cool to 0° C. 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, 10-100%) to give the title compound as a white foam (1.3 g, 3.74 mmol). MS (m/z): 348 (M+1).

Workup

  1. temperatureCool to 0° C
  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-b4c323f4936a4911819c7b6fe9d7d021
Source dataset
uspto-grants-2015_02
Patent number
US08962654B2

Reaction notes

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