1-Pyrrolidineethanamine → 4-[3-(2-Pyrrolidin-1-yl-ethylamino)-phenyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 1667516Notes

Reaction equation

HRID 1667516 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16](Br)[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:21]1([CH2:26][CH2:27][NH2:28])[CH2:25][CH2:24][CH2:23][CH2:22]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC([O-])(C)C.[Na+]>O1CCOCC1.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]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([NH:28][CH2:27][CH2:26][N:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 13441-PyrrolidineethanamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 10882380tert-Butyl 4-(3-bromophenyl)piperazine-1-carboxylateHCID 23676156Sodium t-butoxide

Product 1

HCID 674159094-[3-(2-Pyrrolidin-1-yl-ethylamino)-phenyl]-piperazine-1-carboxylic acid tert-butyl esterYield 62%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 4-(3-bromo-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (300 mg, 0.88 mmol), 2-pyrrolidin-1-yl-ethylamine (0.165 mL, 1.32 mmol), Pd2(dba)3 (40 mg, 0.044 mmol), xantphos (50 mg, 0.088 mmol) and NaOt-Bu (124 mg, 1.32 mmol) in dioxane (15 mL) was bubbled with nitrogen in a sealed tube for 10 min. The mixture was heated at 120° C. for 2 h. After this time the mixture was cooled and filtered through celite and concentrated. Chromatography on silica (ethyl acetate/MeOH) provided the title compound (203 mg, 62%). m/z (M+1) 375.53

Workup

  1. customwas bubbled with nitrogen in a sealed tube for 10 min
  2. temperatureAfter this time the mixture was cooled
  3. filtrationfiltered through celite and
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-117f98538b0344118046f47b1fbc7413
Source dataset
uspto-grants-2011_10
Patent number
US08044041B2

Reaction notes

Loading…