Benzylamine → tert-Butyl 1-[3-(benzylamino)-4-chlorobenzyl]cyclopropanecarboxylate

HRID 1475625Notes

Reaction equation

HRID 1475625 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[Cl:19])[CH2:5][C:6]1([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:8][CH2:7]1.[CH2:20]([NH2:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=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>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>[CH2:20]([NH:27][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[Cl:19])[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:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

7

Reactant 4

HCID 7504BenzylamineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 67958496tert-Butyl 1-(3-bromo-4-chlorobenzyl)cyclopropanecarboxylate

Product 1

HCID 68006927tert-Butyl 1-[3-(benzylamino)-4-chlorobenzyl]cyclopropanecarboxylate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

Under argon, 95.0 g (274.8 mmol) of tert-butyl 1-(3-bromo-4-chlorobenzyl)cyclopropanecarboxylate, 36.0 ml (330.0 mmol) of benzylamine, 12.58 g (13.7 mmol) of tris(dibenzylideneacetone)dipalladium, 31.69 g (329.8 mmol) of sodium tert-butoxide and 6.85 g (5.29 mmol) of (+/−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl were added in succession to 633 ml of dry toluene. The reaction mixture was stirred at 110° C. for 3.0 h and then at RT overnight. The reaction mixture was then filtered off with suction through kieselguhr, and the residue was washed thoroughly with toluene and ethyl acetate. The combined filtrates were concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (mobile phase petroleum ether/ethyl acetate 10:1). This gave 50.0 g of the title compound (48.9% of theory).

Workup

  1. customat RT
  2. customovernight
  3. filtrationThe reaction mixture was then filtered off with suction through kieselguhr
  4. washthe residue was washed thoroughly with toluene and ethyl acetate
  5. concentrationThe combined filtrates were concentrated under reduced pressure
  6. customThe crude product was purified by chromatography on silica gel (mobile phase petroleum ether/ethyl acetate 10:1)

Sources & evidence

ORD record
ord-68528a99bd5547c29d50c926df13303c
Source dataset
uspto-grants-2015_04
Patent number
US09018258B2

Reaction notes

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