Tributylamine → 3-[2-(tert-Butoxycarbonylamino-methyl)-phenyl]-but-2-enoic Acid Ethyl Ester

HRID 2249494Notes

Reaction equation

HRID 2249494 reaction equation
[C:1]([NH:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1Br)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C(N(CCCC)CCCC)CCC.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[CH2:52]([O:54][C:55](=[O:59])/[CH:56]=[CH:57]/[CH3:58])[CH3:53]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:52]([O:54][C:55](=[O:59])[CH:56]=[C:57]([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=1[CH2:9][NH:8][C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH3:58])[CH3:53]

Participants

6

Reactant 4

HCID 7622TributylamineHCID 80271Tri-o-tolylphosphineHCID 429065Ethyl trans-crotonateHCID 70183002-Bromo-N-(tert-butoxycarbonyl)benzylamine

Product 1

HCID 692191913-[2-(tert-Butoxycarbonylamino-methyl)-phenyl]-but-2-enoic Acid Ethyl EsterYield 20%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
110 °C

Procedure

N-Boc-2-bromobenzylamine (7.15 g, 25 mmol) was dissolved into tributylamine (12 mL) and degassed under vacuum. Palladium acetate (224 mg, 1 mmol) and tri-o-tolylphosphine (608 mg, 2 mmol) was then added and the mixture degassed under vacuum. Trans-ethylcrotonate (6.25 mL, 50 mmol) was then added and the mixture was degassed with nitrogen. The tube was sealed and the mixture was heated to 110° C. for 48 h. The solution was cooled to room temperature, diluted with diethyl ether (200 mL) and filtered through celite. The solution was washed with 1N HCl (2×50 mL) and brine (50 mL) dried over magnesium sulfate and concentrated to dryness. Flash chromatography (9:1 hexanes/ethyl acetate) gave the title compound as a yellow oil (1.6 g, 20%). 1H NMR 7.22-7.37 (m, 3H), 7.08 (dd, J=7.4, 1.6 Hz, 1H), 5.75 (d, J=1.3 Hz, 1H), 4.29-4.31 (m, 2H), 4.20 (q, J=7.1 Hz, 2H), 2.45 (d, J=1.3 Hz, 3H), 1.44 (s, 9H), 1.30 (t, J=7.1 Hz, 3H).

Workup

  1. customdegassed under vacuum
  2. customthe mixture degassed under vacuum
  3. customthe mixture was degassed with nitrogen
  4. customThe tube was sealed
  5. temperatureThe solution was cooled to room temperature
  6. additiondiluted with diethyl ether (200 mL)
  7. filtrationfiltered through celite
  8. washThe solution was washed with 1N HCl (2×50 mL) and brine (50 mL)
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-0fecef3430894b41b6f9216bf53b1559
Source dataset
uspto-grants-2008_01
Patent number
US07314879B2

Reaction notes

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