Sodium t-butoxide → HCID 68212263, compound

HRID 540363Notes

Reaction equation

HRID 540363 reaction equation
CC(C)([O-])C.[Na+].Cl[C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][CH:17]=1)[C:14](=[O:18])[N:13]([CH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[CH2:12][CH2:11]2.[CH3:25][C@H:26]1[CH2:30][CH2:29][CH2:28][N:27]1[C@H:31]1[CH2:35][CH2:34][NH:33][CH2:32]1>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>[CH3:25][C@H:26]1[CH2:30][CH2:29][CH2:28][N:27]1[C@H:31]1[CH2:35][CH2:34][N:33]([C:8]2[CH:9]=[C:10]3[C:15](=[CH:16][CH:17]=2)[C:14](=[O:18])[N:13]([CH:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)[CH2:12][CH2:11]3)[CH2:32]1

Participants

7

Reactant 3

HCID 23676156Sodium t-butoxideHCID 59401808(2S,3'S)-2-Methyl-[1,3]bipyrrolidinylHCID 67468989HCID 67468989, compound

Product 1

HCID 68212263HCID 68212263, compoundYield 54.1%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalystHCID 1140TolueneSolvent2×

Procedure

An 8-mL vial containing a stir bar was charged with Pd2(dba)3 (0.01 equiv., 4 pmol, 4 mg.), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl 1 (0.05 equiv., 0.02 mmol, 10 mg) and sodium t-butoxide (2.5 equiv., 1.03 mmol, 99 mg.). To this solution was transferred a solution of 6-chloro-2-(tetrahydro-pyran-4-yl)-3,4-dihydro-2H-isoquinolin-1-one (110 mg, 0.41 mmol) in anhydrous toluene (2 mL) under N2 with stirring at rt. Then, a solution of the (2S,3′S)-2-methyl-[1,3]-bipyrrolidinyl (1.3 equiv., 0.53 mmol, 83 mg) in anhydrous toluene (2 mL) was transferred. The vial was capped with a rubber septum, evacuated and backfilled with N2. To this vial was introduced 2 mL of anhydrous toluene. The reaction was heated in an oil bath set at 90° C. for 5 h, allowed to cool down to room temperature and quenched with water (2 mL). Extraction with ethyl acetate (3×10 mL) followed by chromatography on silica gel column with 0-5% 7N NH3/MeOH in DCM to give 85 mg (54% yield) of the title compound as a yellow solid.

Workup

  1. additionAn 8-mL vial containing a stir bar
  2. customThe vial was capped with a rubber septum
  3. customevacuated
  4. additionTo this vial was introduced 2 mL of anhydrous toluene
  5. temperatureThe reaction was heated in an oil bath
  6. temperatureto cool down to room temperature
  7. customquenched with water (2 mL)
  8. extractionExtraction with ethyl acetate (3×10 mL)

Sources & evidence

ORD record
ord-49d707a3e9994f5987ec92b0660eb811
Source dataset
uspto-grants-2014_10
Patent number
US08871788B2

Reaction notes

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