Toluene → HCID 54596984, compound

HRID 540364Notes

Reaction equation

HRID 540364 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][N:8]([C:12]([CH:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)=[O:13])[CH2:9]2)=[CH:4][CH:3]=1.[CH3:20][C@H:21]1[CH2:25][CH2:24][CH2:23][N:22]1[C@H:26]1[CH2:30][CH2:29][NH:28][CH2:27]1.CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1>CO.C(Cl)Cl.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[CH3:20][C@H:21]1[CH2:25][CH2:24][CH2:23][N:22]1[C@H:26]1[CH2:30][CH2:29][N:28]([C:2]2[CH:11]=[C:10]3[C:5]([CH2:6][CH2:7][N:8]([C:12]([CH:14]4[CH2:19][CH2:18][O:17][CH2:16][CH2:15]4)=[O:13])[CH2:9]3)=[CH:4][CH:3]=2)[CH2:27]1

Participants

8

Reactant 4

HCID 1140TolueneHCID 23676156Sodium t-butoxideHCID 59401808(2S,3'S)-2-Methyl-[1,3]bipyrrolidinylHCID 67466031HCID 67466031, compound

Product 1

HCID 54596984HCID 54596984, compoundYield 53%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
85 °C

Procedure

A vial was charged with (7-bromo-3,4-dihydro-1H-isoquinolin-2-yl)-(tetrahydro-pyran-4-yl)-methanone (162 mg, 0.5 mmol), (2S,3′S)-2-methyl-[1,3′]bipyrrolidinyl (90 mg, 0.55 mmol), and sodium tert-butoxide (69 mg, 0.7 mmol), tris(dibenzylideneacetone)dipalladium-(0) (4.6 mg, 0.005 mmol), BINAP (9.3 mg, 0.015 mmol), and toluene (4 mL) under argon. The vial was capped with a septum and was heated to 85° C. (external) with stirring until the starting material was completely consumed as monitored by TLC analysis. The mixture was allowed to cool to room temperature, taken up in ether (5.0 mL), filtered, and concentrated. The crude product was then purified further by flash chromatography on silica gel, eluted with 3% MeOH in DCM and 7.5% MeOH in DCM to 105 mg (53% yield) of the title compound as a tan solid.

Workup

  1. customThe vial was capped with a septum
  2. customwas completely consumed
  3. temperatureto cool to room temperature
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was then purified further by flash chromatography on silica gel

Sources & evidence

ORD record
ord-955dc7649db44440a19caa49659f92ac
Source dataset
uspto-grants-2014_10
Patent number
US08871788B2

Reaction notes

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