Benzylamine → tert-Butyl 1-[3-(benzylamino)benzyl]cyclopropanecarboxylate

HRID 1475618Notes

Reaction equation

HRID 1475618 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][CH:18]=1)[CH2:5][C:6]1([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:8][CH2:7]1.[CH2:19]([NH2:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.CC(C)([O-])C.[Na+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>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]>[CH2:19]([NH:26][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][CH:18]=1)[CH2:5][C:6]1([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:8][CH2:7]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

7

Reactant 4

HCID 7504BenzylamineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 58136610tert-Butyl 1-(3-bromobenzyl)cyclopropanecarboxylate

Product 1

HCID 58136299tert-Butyl 1-[3-(benzylamino)benzyl]cyclopropanecarboxylate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

Under argon and dry conditions, 13.3 g (42.73 mmol) of tert-butyl 1-(3-bromobenzyl)-cyclopropanecarboxylate, 5.6 ml (51.28 mmol) of benzylamine, 1.96 g (2.14 mmol) of tris(dibenzylideneacetone)dipalladium, 4.93 g (51.28 mmol) of sodium tert-butoxide and 1.06 g (1.71 mmol) of (+/−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl were suspended in 50 ml of toluene. The reaction mixture was then stirred at 110° C. for 1.5 h. The mixture was then filtered off with suction through kieselguhr, the residue was washed with toluene and the filtrate was concentrated. The filtrate residue was taken up in ethyl acetate and washed twice with aqueous ammonium chloride solution. The organic phase was dried over magnesium sulphate and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 20:1). This gave 6.98 g (48.4% of theory) of the title compound.

Workup

  1. filtrationThe mixture was then filtered off with suction through kieselguhr
  2. washthe residue was washed with toluene
  3. concentrationthe filtrate was concentrated
  4. washwashed twice with aqueous ammonium chloride solution
  5. dry with materialThe organic phase was dried over magnesium sulphate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 20:1)

Sources & evidence

ORD record
ord-7e52cb3843cd4d4787f4985b38369b21
Source dataset
uspto-grants-2015_04
Patent number
US09018258B2

Reaction notes

Loading…