Triethylamine → Benzenepropanoic acid, 4-(cyanomethyl)-, 1,1-dimethylethyl ester

HRID 1087004Notes

Reaction equation

HRID 1087004 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]#[N:10])=[CH:4][CH:3]=1.[C:11]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])(=[O:14])[CH:12]=[CH2:13].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>C(OCC)(=O)C.C([O-])(=O)C.C([O-])(=O)C.[Pd+2]>[C:16]([O:15][C:11]([CH2:12][CH2:13][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]#[N:10])=[CH:4][CH:3]=1)=[O:14])([CH3:19])([CH3:18])[CH3:17]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 15458tert-Butyl acrylateHCID 27914Benzeneacetonitrile, 4-bromo-HCID 80271Tri-o-tolylphosphine

Product 1

HCID 9992094Benzenepropanoic acid, 4-(cyanomethyl)-, 1,1-dimethylethyl ester

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 5 g of p-bromophenylacetonitrile, 4.6 ml of t-butyl acrylate, 57 mg of palladium diacetate, 310 mg of tri-o-tolylphosphine and 12 ml of triethylamine is refluxed for 5 hours. The reaction mixture is diluted with ethyl acetate and washed with 10% HCl and saturated sodium bicarbonate solution. After drying over magnesium sulfate the solvent is removed in vacuo. This material is dissolved in ethanol and hydrogenated over 1.1 g of 10% palladium on carbon catalyst for 3 days at 3 atmospheres pressure of hydrogen. After filtration the solvent is removed in vacuo and the residue is chromatographed on silica gel with ether/hexane (1:1) as the eluent to afford p-(2-t-butoxycarbonyl-ethyl)-phenylacetonitrile; 2.8 g of this product is dissolved in 90 ml of tetrahydrofuran and 50 ml of methanol and to this is added 6.2 g of cobalt chloride in 90 ml of water followed by 2.1 g of sodium borohydride in small portions. After filtration and removal of solvent, the residue is chromatographed on silica gel with 7.5% methanol saturated with ammonia in methylene chloride as the eluent to afford p-(2-t-butoxycarbonyl-ethyl)-2-phenethylamine as an oil.

Workup

  1. temperatureis refluxed for 5 hours
  2. washwashed with 10% HCl and saturated sodium bicarbonate solution
  3. dry with materialAfter drying over magnesium sulfate the solvent
  4. customis removed in vacuo
  5. dissolutionThis material is dissolved in ethanol
  6. filtrationAfter filtration the solvent
  7. customis removed in vacuo
  8. customthe residue is chromatographed on silica gel with ether/hexane (1:1) as the eluent

Sources & evidence

ORD record
ord-f9c49a890ecb4ce2a58807e503741ad5
Source dataset
uspto-grants-1991_07
Patent number
US05034381

Reaction notes

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