Pyrrolidine → HCID 89676975, compound

HRID 2278240Notes

Reaction equation

HRID 2278240 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)=[C:4]([CH:22]([CH3:24])[CH3:23])[CH:3]=1.[NH:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1.C(O[Na])(C)(C)C.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>O.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(C)C=CC=CC=1>[CH3:23][CH:22]([C:4]1[CH:3]=[C:2]([N:25]2[CH2:29][CH2:28][CH2:27][CH2:26]2)[CH:7]=[CH:6][C:5]=1[CH2:8][N:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]1)[CH3:24]

Participants

8

Reactant 4

HCID 31268PyrrolidineHCID 634876Binap, (A+-)-HCID 89676839HCID 89676839, compoundHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 89676975HCID 89676975, compoundYield 61.5%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A 50 mL round-bottom flask was charged with tert-butyl 4-[[4-bromo-2-(propan-2-yl)phenyl]methyl]piperazine-1-carboxylate (50.0 mg, 0.130 mmol, 1.00 equiv), pyrrolidine (11.0 mg, 0.150 mmol, 1.20 equiv), t-BuONa (17.5 mg, 0.180 mmol, 1.45 equiv), Pd2(dba)3 (6.00 mg, 0.010 mmol, 0.050 equiv), BINAP (12.0 mg, 0.020 mmol, 0.15 equiv), toluene (2 mL). The resulting solution was stirred overnight at 80° C. with an inert atmosphere of nitrogen and then diluted with water (5 mL). The resulting solution was extracted with dichloromethane (3×5 mL) and the organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographed on a silica gel column with ethyl acetate/petroleum ether (20/80) to provide 31.0 mg (61% yield) of tert-butyl 4-[[2-(propan-2-yl)-4-(pyrrolidin-1-yl)phenyl]methyl]piperazine-1-carboxylate as light yellow oil. LCMS (ESI, m/z): 338 [M+H]+.

Workup

  1. extractionThe resulting solution was extracted with dichloromethane (3×5 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was chromatographed on a silica gel column with ethyl acetate/petroleum ether (20/80)

Sources & evidence

ORD record
ord-d9b9723ea7ed41a48b8952d39de82894
Source dataset
uspto-grants-2015_09
Patent number
US09133148B2

Reaction notes

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