Benzylamine → (+/-)-tert-Butyl 1-{[3-(benzylamino)-4-chlorophenyl](methoxy)methyl}cyclopropanecarboxylate

HRID 1475669Notes

Reaction equation

HRID 1475669 reaction equation
CC(C)([O-])C.[Na+].[CH2:7]([NH2:14])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.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.Br[C:62]1[CH:63]=[C:64]([CH:69]([O:80][CH3:81])[C:70]2([C:73]([O:75][C:76]([CH3:79])([CH3:78])[CH3:77])=[O:74])[CH2:72][CH2:71]2)[CH:65]=[CH:66][C:67]=1[Cl:68].[Cl-].[NH4+]>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].C(OCC)(=O)C.C1(C)C=CC=CC=1>[CH2:7]([NH:14][C:66]1[CH:65]=[C:64]([CH:69]([O:80][CH3:81])[C:70]2([C:73]([O:75][C:76]([CH3:77])([CH3:78])[CH3:79])=[O:74])[CH2:71][CH2:72]2)[CH:63]=[CH:62][C:67]=1[Cl:68])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

9

Reactant 5

HCID 7504BenzylamineHCID 25517Ammonium ChlorideHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 68170327(+/-)-tert-Butyl 1-[(3-bromo-4-chlorophenyl)(methoxy)methyl]cyclopropanecarboxylate

Product 1

HCID 68170328(+/-)-tert-Butyl 1-{[3-(benzylamino)-4-chlorophenyl](methoxy)methyl}cyclopropanecarboxylate

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

In a dry reaction flask which had been flushed with argon, 4.60 g (47.9 mmol) of sodium tert-butoxide were suspended in 100 ml of abs. toluene, and 5.2 ml (47.9 mmol) of benzylamine, 0.99 g (1.6 mmol) of rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl, 1.83 g (2.0 mmol) of tris(dibenzylideneacetone)dipalladium and 15.0 g (39.9 mmol) of (+/−)-tert-butyl 1-[(3-bromo-4-chlorophenyl)(methoxy)methyl]cyclopropanecarboxylate were added. The reaction mixture was heated at 110° C. for 3 h. After cooling, ethyl acetate and saturated aqueous ammonium chloride solution were added and the mixture was filtered through Celite. The organic phase was washed with saturated ammonium chloride solution and saturated sodium chloride solution, dried over magnesium sulphate and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 40:1→20:1). This gave 12.0 g of the target compound (74.8% of theory).

Workup

  1. customIn a dry reaction flask which
  2. temperatureAfter cooling
  3. filtrationthe mixture was filtered through Celite
  4. washThe organic phase was washed with saturated ammonium chloride solution and saturated sodium chloride solution
  5. dry with materialdried over magnesium sulphate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 40:1→20:1)

Sources & evidence

ORD record
ord-fb3a6adb6a9a4ce08935de33e37cd4ce
Source dataset
uspto-grants-2015_04
Patent number
US09018258B2

Reaction notes

Loading…