Trifluoroacetic acid → (S)-5-(1,3-dioxoisoindolin-2-yl)-2-hydroxypentanoic acid

A solution of (S)-2-(tert-butoxycarbonylamino)-5-(1,3-dioxoisoindolin-2-yl)pentanoic acid L (1.45 g, 4.0 mmol) in dichloroethane (25 mL) was cooled to 0° C. Trifluoroacetic acid was added in one portion and the mixture was allowed to warm to room temperature and stir for 2 h. The mixture was concentrated to dryness mixed with water (18.5 mL), HOAc (9.5 mL) and aqueous NaNO2 (1.2 g in 25 mL H2O). After 15 min another portion of HOAc (14 mL) was added and the mixture was stirred at room temperature for 18 h. The reaction mixture was concentrated to dryness. The residue was dissolved in water (100 mL), the pH was adjusted to 1 by addition of 10% aqueous HCl, and the solution was extracted with diethyl ether (5×100 mL). The organic phase was dried over Na2SO4 and concentrated to dryness under reduced pressure afford (S)-5-(1,3-dioxoisoindolin-2-yl)-2-hydroxypentanoic acid LI (0.98 g, 3.73 mmol, 93%). ESIMS found for C13H13NO5 m/z 262 (M−H)−.

1. concentrationThe mixture was concentrated to dryness
2. additionmixed with water (18.5 mL), HOAc (9.5 mL) and aqueous NaNO2 (1.2 g in 25 mL H2O)
3. additionAfter 15 min another portion of HOAc (14 mL) was added
4. stirringthe mixture was stirred at room temperature for 18 h
5. concentrationThe reaction mixture was concentrated to dryness
6. dissolutionThe residue was dissolved in water (100 mL)
7. additionthe pH was adjusted to 1 by addition of 10% aqueous HCl
8. extractionthe solution was extracted with diethyl ether (5×100 mL)
9. dry with materialThe organic phase was dried over Na2SO4
10. concentrationconcentrated to dryness under reduced pressure

ORD record

ord-d829e26d12a349b98a58ee149a2da272

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08906868B2