Triethylamine → 1-(3,4-Difluorobenzoyl)azetidine

3,4-Difluorobenzoic acid (1.03 g, 6.51 mmol) in CH2Cl2 (10 ml) was added SOCl2 (600 uL, 8.26 mmol) and DMF (3 drop). The reaction mixture was heated to reflux for 3 hr. The mixture was evaporated under vacuum and dried. The oil/solid mixture was taken into CH2Cl2 (20 mL) and added azetidine hydrochloride (731 mg, 7.82 mmol) and triethylamine (2.75 mL, 19.7 mmol). The reaction mixture was stirred at room temperature for 2 hr, quenched with 1 N HCl (60 mL) and extracted with EtOAc. The organic layers were dried over MgSO4 and concentrated to give pale yellow oil which was purified by flash column chromatography eluting with 30% EtOAc in hexanes to give a white solid (553 mg, 48% yield). 1H NMR (400 MHz, CDCl3) δ 7.50 (m, 1 H) 7.40 (m 1 H) 7.16-7.25 (m, 1 H) 4.32 (d, J=6.82 Hz, 2 H) 4.24 (d, J=7.07 Hz, 2 H) 2.33-2.42 (m, 2 H).

1. temperatureThe reaction mixture was heated
2. temperatureto reflux for 3 hr
3. customThe mixture was evaporated under vacuum
4. customdried
5. customquenched with 1 N HCl (60 mL)
6. extractionextracted with EtOAc
7. dry with materialThe organic layers were dried over MgSO4
8. concentrationconcentrated
9. customto give pale yellow oil which
10. customwas purified by flash column chromatography
11. washeluting with 30% EtOAc in hexanes

ORD record

ord-381b87154ad240268b5ee1ae934b9375

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08119624B2