Benzoyl chloride → 3-[2-(Benzoylamino-methyl)4-hydroxy-phenyl]propionic acid tert-butyl ester

HRID 1181047Notes

Reaction equation

HRID 1181047 reaction equation
[C:1]([O:5][C:6](=[O:18])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][C:10]=1[CH2:16][NH2:17])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[C:26](Cl)(=[O:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C(Cl)Cl>[C:1]([O:5][C:6](=[O:18])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][C:10]=1[CH2:16][NH:17][C:26](=[O:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 7412Benzoyl chlorideHCID 8471TriethylamineHCID 17984622Tert-butyl-3-[2-(aminomethyl)-4-hydroxyphenyl]propanoate

Product 1

HCID 589795203-[2-(Benzoylamino-methyl)4-hydroxy-phenyl]propionic acid tert-butyl esterYield 64%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A slurry of 3-(2-aminomethyl-4-hydroxy-phenyl)-propionic acid tert-butyl ester (0.36 g, 1.43 mmol) in CH2Cl2 (10 mL) was cooled in an ice-water bath and treated with triethyl amine (0.40 mL, 0.28 mmol) then dropwise with benzoyl chloride (0.18 mL, 1.55 mmol). The resulting solution was stirred 30 min, and the cooling bath was removed. After 30 min, the solution was concentrated, and the residue was partitioned between EtOAc (50 mL) and 1N HCl (10 mL). The organic layer was washed with brine (10 mL), dried (Na2SO4), and concentrated to a solid. The crude mixture was purified by radial chromatography (hexanes:EtOAc 3:1 to 2:1) to give the title compound as a white solid (325 mg, 64%): 1H NMR (400 MHz, CDCl3) 1.26 (s, 9H), 2.54 (t, J=7.1 Hz, 2H), 2.81 (t, J=6.8 Hz, 2H), 4.55 (d, J=2H), 6.68 (dd, J=8.3, 2.4 Hz, 1H), 6.86 (d, J=2.9 Hz, 1H), 6.96 (d, J=8.3 Hz, 1H), 7.25-7.29 (m, 2H), 7.34-7.37 (m, 1H), 7.49 (br s, 1H), 7.16-7.79 (m, 2H); MS (ES) m/z 356.2 (M+H).

Workup

  1. customthe cooling bath was removed
  2. waitAfter 30 min
  3. concentrationthe solution was concentrated
  4. customthe residue was partitioned between EtOAc (50 mL) and 1N HCl (10 mL)
  5. washThe organic layer was washed with brine (10 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated to a solid
  8. customThe crude mixture was purified by radial chromatography (hexanes:EtOAc 3:1 to 2:1)

Sources & evidence

ORD record
ord-ac6b2ac2f6264921b01f6f22b88755ca
Source dataset
uspto-grants-2007_10
Patent number
US07282501B2

Reaction notes

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