Cesium carbonate → (3-Pyrrolidin-1-ylphenyl)methylamine

HRID 2041161Notes

Reaction equation

HRID 2041161 reaction equation
C(OC(=O)[NH:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11](Br)[CH:10]=1)(C)(C)C.[NH:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1.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.C(=O)([O-])[O-].[Cs+].[Cs+]>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]>[N:17]1([C:11]2[CH:10]=[C:9]([CH:14]=[CH:13][CH:12]=2)[CH2:8][NH2:7])[CH2:21][CH2:20][CH2:19][CH2:18]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 31268PyrrolidineHCID 634876Binap, (A+-)-HCID 11033439tert-Butyl 3-bromobenzylcarbamate

Product 1

HCID 7162061(3-Pyrrolidin-1-ylphenyl)methylamineYield 85%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

Slurry a mixture of (3-bromobenzyl)-carbamic acid tert-butyl ester (600 mg, 2.1 mmol, U.S. Pat. Appl. Publ. US 2003134885), pyrrolidine (450 mL, 5.2 mmol), tris(dibenzylideneacetone)dipalladium(0) (200 mg, 0.21 mmol), BINAP (400 mg, 0.63 mmol) and cesium carbonate (960 mg, 2.94 mmol) in anhydrous toluene (10 mL). Degas under vacuum, fill the system with nitrogen and heat in a sealed flask at 90° C. for 18 h. Cool to room temperature, dilute with diethyl ether, filter, and concentrate in vacuo. Dissolve the resulting residue in DCM (10 mL) and add trifluoroacetic acid (5 mL). Stir at ambient temperature for 1 h and concentrate in vacuo. Purify by chromatography on silica gel eluting sequentially with hexane/EtOAc (1:1), EtOAc and 2M ammonia in methanol. Purify again by SCX chromatography to give the title compound as a brown oil (300 mg, 85% overall). MS (ES+) m/z: 178 (M+H)+.

Workup

  1. customDegas under vacuum
  2. temperatureCool to room temperature
  3. additiondilute with diethyl ether
  4. filtrationfilter
  5. concentrationconcentrate in vacuo
  6. dissolutionDissolve the resulting residue in DCM (10 mL)
  7. additionadd trifluoroacetic acid (5 mL)
  8. concentrationconcentrate in vacuo
  9. customPurify by chromatography on silica gel eluting sequentially with hexane/EtOAc (1:1), EtOAc and 2M ammonia in methanol
  10. customPurify again by SCX chromatography

Sources & evidence

ORD record
ord-c01dd05d07184fe68ce9b050a246afe3
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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