Chloroform → Tert-butyl 2-(4-aminophenyl)pyrrolidine-1-carboxylate

HRID 2236507Notes

Reaction equation

HRID 2236507 reaction equation
[Li+].C[Si]([N-:6][Si](C)(C)C)(C)C.C(Cl)(Cl)Cl.P(C(C)(C)C)(C(C)(C)C)C(C)(C)C.[H+].[B-](F)(F)(F)F.[C:34]([O:38][C:39]([N:41]1[CH2:45][CH2:44][CH2:43][CH:42]1[C:46]1[CH:51]=[CH:50][C:49](Br)=[CH:48][CH:47]=1)=[O:40])([CH3:37])([CH3:36])[CH3:35]>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>[C:34]([O:38][C:39]([N:41]1[CH2:45][CH2:44][CH2:43][CH:42]1[C:46]1[CH:51]=[CH:50][C:49]([NH2:6])=[CH:48][CH:47]=1)=[O:40])([CH3:37])([CH3:36])[CH3:35]

Participants

8

Reactant 5

HCID 6212ChloroformHCID 28118Tetrafluoroboric acidHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 2733832Lithium HexamethyldisilazideHCID 53407516tert-Butyl 2-(4-bromophenyl)pyrrolidine-1-carboxylate

Product 1

HCID 44607625Tert-butyl 2-(4-aminophenyl)pyrrolidine-1-carboxylateYield 83%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

LiHMDS (1.6 g, 9.6 mmol) is added to a 100 mL round bottom flask. Toluene (20 mL) is added followed by addition of Pd2(dba)3.CHCl3 (50 mg, 0.05 mmol) and P(tBu)3.HBF4 (40 mg, 0.14 mmol). 2-(4-Bromo-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.5 g, 4.6 mmol) is added to the flask. After degasing, the mixture is stirred at room temperature overnight. After TLC suggested no starting bromide is left, the reaction mixture is diluted with ether and poured into dilute HCl (aq). The ether layer is discarded, the aqueous layer is basified with NH4OH and extracted with EtOAc. The EtOAc layer is dried and concentrated to provide the desired product (1.0 g, 83%). 1H NMR (300 MHz, CDCl3) ∂ 6.94-6.96 (2H, m), 6.60-6.67 (2H, m), 4.67-4.85 (1H, m), 3.58 (4H, br), 2.24 (1H, m), 1.73-1.97 (3H, m), 1.44 (3H, s), 1.21 (6H, s).

Workup

  1. customAfter degasing
  2. waitis left
  3. additionthe reaction mixture is diluted with ether
  4. additionpoured into dilute HCl (aq)
  5. extractionextracted with EtOAc
  6. dry with materialThe EtOAc layer is dried
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-791a14add560472c9c4d37d86e6eb5b9
Source dataset
uspto-grants-2010_05
Patent number
US07713994B2

Reaction notes

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