Triphenylphosphine → methyl (S)-3-chloro-4-(2-amino-1-propoxy)benzoate

To a cooled (0° C.) solution of (S)-2-(N-tert-butoxycarbonylamino)-1-propanol (1.05 g, 5.99 mmol), methyl 3-chloro-4-hydroxybenzoate (1.12 g, 6.00 mmol), and Ph3P (2.36 g, 9.00 mmol) in THF (20 mL) was added diisopropyl azodicarboxylate (DIAD) (1.77 mL, 8.99 mmol), and the resulting mixture was heated under reflux for 2 days. The solution was evaporated off and the residue was dissolved in CH2Cl2 (20 mL) and TFA (10 mL). The resulting mixture was stirred at room temp for 1.5 hr. The solution was concentrated in vacuo, and the residue was dissolved in CHCl3. The mixture was extracted with H2O, and the aqueous layer was made basic by the addition of sat. NaHCO3. This basic aqueous layer was extracted with CHCl3. The extract was washed with brine, dried over Na2SO4 and evaporated to give 660 mg (2 steps, 32%) methyl (S)-3-chloro-4-(2-amino-1-propoxy)benzoate as a colorless oil. 1H-NMR (CDCl3) δ 1.21 (d, 3 H, J=6.4 Hz), 3.41–3.48 (m, 1 H), 3.77–3.81 (m, 1 H), 3.89 (s, 3 H), 3.98–4.01 (m, 1 H), 6.91–6.94 (m, 1 H), 7.90–7.93 (m, 1 H), 8.05–8.06 (m, 1 H).

1. temperaturethe resulting mixture was heated
2. temperatureunder reflux for 2 days
3. customThe solution was evaporated off
4. dissolutionthe residue was dissolved in CH2Cl2 (20 mL)
5. concentrationThe solution was concentrated in vacuo
6. dissolutionthe residue was dissolved in CHCl3
7. extractionThe mixture was extracted with H2O
8. additionthe aqueous layer was made basic by the addition of sat. NaHCO3
9. extractionThis basic aqueous layer was extracted with CHCl3
10. washThe extract was washed with brine
11. dry with materialdried over Na2SO4
12. customevaporated

ORD record

ord-a8d8d4e4546548a1984e3697f8c32deb

Source dataset

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07179819B2