Ammonium Chloride → HCID 59504645, compound

Temperature

-78 °C

To a solution of 4-iodobenzonitrile (5.0 g, 21.8 mmol) in dry THF (100 mL) was added 2-propyl magnesium chloride (2M solution in diethyl ether, 11 mL, 21.8 mmol) dropwise at −40° C. After stirring for 1.5 h at this temperature, the reaction mixture was cooled to −78° C. before it was canulated to a solution of 3-oxooxetane (80% in dichloromethane, 2.95 g, 32.7 mmol; preparation described in: G. Wuitschik et al., Angew. Chem. Int. Ed. Engl. 45 (46), 7736-7739 (2006)) in dry THF (100 mL) which was likewise cooled to −78° C. After the slow addition of the Grignard reagent was completed, the reaction mixture was stirred at −78° C. for additional 10 minutes, then at 0° C. for 2 h, and finally at rt for 30 minutes. A few mL saturated aqueous NH4Cl were added and then most of the solvent was evaporated. The residue was partitioned between water and ethyl acetate (200 mL each). After separation, the aqueous layer was extracted using ethyl acetate. The combined organic layers were successively washed with water and brine. After drying over anhydrous magnesium sulfate, the solvent was evaporated and the crude material was crystallized from cyclohexane/ethyl acetate 10:1. The title compound was obtained in pure form (2.42 g, 63%): 1H NMR (400 MHz, DMSO-d6) δ 7.88 (d, 2H), 7.80 (d. 2H), 6.63 (s, 1H), 4.79 (d, 2H), 4.65 (d, 2H); DCI(NH3)-MS m/z 193 (M+NH4)+; HPLC RT (Method I) 3.09 min.

1. temperaturewas likewise cooled to −78° C
2. stirringthe reaction mixture was stirred at −78° C. for additional 10 minutes
3. waitat 0° C. for 2 h
4. waitfinally at rt for 30 minutes
5. custommost of the solvent was evaporated
6. customThe residue was partitioned between water and ethyl acetate (200 mL each)
7. customAfter separation
8. extractionthe aqueous layer was extracted
9. washThe combined organic layers were successively washed with water and brine
10. dry with materialAfter drying over anhydrous magnesium sulfate
11. customthe solvent was evaporated
12. customthe crude material was crystallized from cyclohexane/ethyl acetate 10:1

ORD record

ord-0f978613e7df4e9e8ac5a6cc8261173f

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08796253B2