3-Bromobenzonitrile → 3-pyrrolidin-1-ylbenzonitrile

HRID 1167301Notes

Reaction equation

HRID 1167301 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[C:5]#[N:6].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+].[NH:62]1[CH2:66][CH2:65][CH2:64][CH2:63]1>O1CCCC1.C(OCC)C.O>[N:62]1([C:2]2[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=2)[C:5]#[N:6])[CH2:66][CH2:65][CH2:64][CH2:63]1

Participants

8

Reactant 4

HCID 233813-BromobenzonitrileHCID 31268PyrrolidineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxide

Product 1

HCID 71623323-pyrrolidin-1-ylbenzonitrileYield 5.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

A reaction mixture of 3-bromo-benzonitrile (0.91 g, 5 mmol), tris(dibenzylidenecetone)-dipalladium (229 mg), (S)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (311 mg, 0.5 mmol), sodium tert-butoxide (740 mg, 7.7 mmol), pyrrolidine (0.58 mL, 6.9 mmol) in tetrahydrofuran (10 mL) was heated at 80° C. in a sealed tube for 6 h. The reaction mixture was worked up with water and diethyl ether. The organic layers were washed with brine and dried over anhydrous magnesium sulfate. The solid was then filtered off, and the filtrate was concentrated in vacuo. Purification of the crude residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel) eluting with 0-5% ethyl acetate in hexanes yielded 3-pyrrolidin-1-yl-benzonitrile (45 mg, 5%).

Workup

  1. washThe organic layers were washed with brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. filtrationThe solid was then filtered off
  4. concentrationthe filtrate was concentrated in vacuo
  5. customPurification of the crude residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel)
  6. washeluting with 0-5% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-50de50b618b444b6936f0c49cef43f12
Source dataset
uspto-grants-2003_09
Patent number
US06617346B1

Reaction notes

Loading…