Methylparaben → methyl (S)-4-(2-amino-1-propoxy)benzoate

To a cooled (0° C.) solution of (S)-2-(N-tert-butoxycarbonylamino)-1-propanol (1.02 g, 5.82 mmol), methyl 4-hydroxybenzoate (0.89 g, 5.85 mmol), and Ph3P (1.98 g, 7.55 mmol) in THF (20 mL) was added diisopropyl azodicarboxylate (DIAD) (1.49 mL, 7.57 mmol), and the resulting mixture was heated under reflux overnight. The solution was evaporated and the residue was dissolved in CH2Cl2 (20 mL) and TFA (10 mL). The mixture was stirred at room temp for 1.5 hr. The solution was concentrated in vacuo and the residue was treated with sat. NaHCO3. The mixture was extracted with CHCl3, washed with brine, dried over Na2SO4 and evaporated. The residue was purified by column chromatography on silica-gel with CHC3:MeOH (50:1, v/v) to give 480 mg (2 steps 39%) methyl (S)-4-(2-amino-1-propoxy)benzoate as a pale yellow oil. 1H-NMR (CDCl3) δ1.19 (d, 3 H, J=6.4 Hz), 3.35-3.39 (m, 1 H), 3.72-3.76 (m, 1 H), 3.89 (s, 3 H), 3.90-3.94 (m, 1 H), 6.92 (d, 2 H, J=8.8 Hz), 7.99 (d, 2 H, J=8.8 Hz).

1. temperaturethe resulting mixture was heated
2. temperatureunder reflux overnight
3. customThe solution was evaporated
4. dissolutionthe residue was dissolved in CH2Cl2 (20 mL)
5. concentrationThe solution was concentrated in vacuo
6. additionthe residue was treated with sat. NaHCO3
7. extractionThe mixture was extracted with CHCl3
8. washwashed with brine
9. dry with materialdried over Na2SO4
10. customevaporated
11. customThe residue was purified by column chromatography on silica-gel with CHC3

ORD record

ord-f2d8d065f0c14ef2a84cea817ade5459

Source dataset

uspto-grants-2004_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06756378B2