HCID 21975858, compound → 6-((2S,3'S)-2-Methyl-[1,3']bipyrrolidinyl-1'-yl)-2-(toluene-4-sulfonyl)-1,2,3,4-tetrahydro-isoquinoline

HRID 467557Notes

Reaction equation

HRID 467557 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH2:8][N:7]([S:12]([C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=1)(=[O:14])=[O:13])[CH2:6][CH2:5]2.CC([O-])(C)C.[Na+].[CH3:28][C@H:29]1[CH2:33][CH2:32][CH2:31][N:30]1[C@H:34]1[CH2:38][CH2:37][NH:36][CH2:35]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].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>[CH3:28][C@H:29]1[CH2:33][CH2:32][CH2:31][N:30]1[C@H:34]1[CH2:38][CH2:37][N:36]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[CH2:8][N:7]([S:12]([C:15]2[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=2)(=[O:14])=[O:13])[CH2:6][CH2:5]3)[CH2:35]1

Participants

7

Reactant 3

HCID 21975858HCID 21975858, compoundHCID 23676156Sodium t-butoxideHCID 59401808(2S,3'S)-2-Methyl-[1,3]bipyrrolidinyl

Product 1

HCID 682110156-((2S,3'S)-2-Methyl-[1,3']bipyrrolidinyl-1'-yl)-2-(toluene-4-sulfonyl)-1,2,3,4-tetrahydro-isoquinolineYield 78%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

6-Bromo-2-(toluene-4-sulfonyl)-1,2,3,4-tetrahydro-isoquinoline (4.32 g, 11.8 mmol, 1 eq), NaOt-Bu (1.64 g, 17.11 mmol, 1.45 eq), Pd2(dba)3 (110 mg, 0.12 mmol, 0.01 eq) and BINAP (221 mg, 0.354 mmol, 0.03 eq) were combined in a round-bottomed flask and purged with nitrogen. 30 mL of dry toluene was added and the solution became red slurry. To this was added a solution of (2S,3′S)-2-Methyl-[1,3′]bipyrrolidinyl (2 g, 13 mmol, 1.1 eq) in 30 mL of dry toluene. The reaction mixture was heated to 85° C. and stirred overnight. The reaction mixture was cooled to rt and quenched with 50 mL of water. This was transferred to a separatory funnel along with 100 mL of brine. The organics were extracted with ethyl acetate (2×100 mL), where they were combined, dried over Na2SO4, concentrated under vacuum and purified by column chromatography on silica gel (200 g column; 50 mL/min; 5% MeOH in CH2Cl2), which afforded 4.02 g (78%) of the title compound as an orange solid.

Workup

  1. custompurged with nitrogen
  2. addition30 mL of dry toluene was added
  3. temperatureThe reaction mixture was cooled to rt
  4. customquenched with 50 mL of water
  5. customThis was transferred to a separatory funnel along with 100 mL of brine
  6. extractionThe organics were extracted with ethyl acetate (2×100 mL), where they
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated under vacuum
  9. custompurified by column chromatography on silica gel (200 g column; 50 mL/min; 5% MeOH in CH2Cl2), which

Sources & evidence

ORD record
ord-fa805b05883a41b598f121bbe5efa4b7
Source dataset
uspto-grants-2014_01
Patent number
US08623877B2

Reaction notes

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