Benzylamine → (+/-)-Tert-butyl 2-[3-(benzylamino)-4-chlorobenzyl]-2-methylbutanoate

HRID 1476098Notes

Reaction equation

HRID 1476098 reaction equation
CC(C)([O-])C.[Na+].[C:7]([O:11][C:12](=[O:26])[C:13]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[C:20](Br)[CH:19]=1)([CH3:16])[CH2:14][CH3:15])([CH3:10])([CH3:9])[CH3:8].[CH2:27]([NH2:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=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.[Cl-].[NH4+]>C(OCC)(=O)C.C1(C)C=CC=CC=1>[CH2:27]([NH:34][C:20]1[CH:19]=[C:18]([CH:23]=[CH:22][C:21]=1[Cl:24])[CH2:17][C:13]([CH3:16])([CH2:14][CH3:15])[C:12]([O:11][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:26])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

8

Reactant 5

HCID 7504BenzylamineHCID 25517Ammonium ChlorideHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 58288436(+/-)-Tert-butyl 2-(3-bromo-4-chlorobenzyl)-2-methylbutanoate

Product 1

HCID 58288180(+/-)-Tert-butyl 2-[3-(benzylamino)-4-chlorobenzyl]-2-methylbutanoate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

Under argon, 1.59 g (16.6 mmol) of sodium tert-butoxide were weighed out into a dry flask, and 34.6 ml of abs. toluene were added. 5.0 g (13.8 mmol) of (+/−)-tert-butyl-2-(3-bromo-4-chlorobenzyl)-2-methylbutanoate, 1.8 ml (16.6 mmol) of benzylamine, 633 mg (0.69 mmol) of tris(dibenzylidenacetone)dipalladium and 344 mg (0.55 mmol) of (+/−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl were added in succession. The reaction mixture was then stirred at 110° C. for 2.0 h. After cooling, saturated aqueous ammonium chloride solution and ethyl acetate were added and the reaction mixture was filtered off with suction through kieselguhr. After phase separation, the organic phase was washed with sat ammonium chloride solution and sat. 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 80:1). This gave 4.44 g of the title compound in still slightly contaminated form (about 83% of theory).

Workup

  1. temperatureAfter cooling
  2. filtrationthe reaction mixture was filtered off with suction through kieselguhr
  3. customAfter phase separation
  4. washthe organic phase was washed with sat ammonium chloride solution and sat. 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 80:1)

Sources & evidence

ORD record
ord-aa55ec484ebc4fa38d665627ae995996
Source dataset
uspto-grants-2015_04
Patent number
US09018414B2

Reaction notes

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