1,2-Dichloroethane → HCID 135749954, compound

To a 20 mL flask was added the crude acid from step 3 (20 mg, 0.1 mmol), HOBt (16 mg, 0.12 mmol), and EDC (23 mg, 0.12 mmol). To this was added dichloromethane (3 mL) and the resulting heterogeneous mixture was stirred for 30 minutes at room temperature. To the resulting solution was added cyclopropylamine (9.0 mg, 0.15 mmol) and the reaction was monitored by HPLC for product formation. After 2 hours, the reaction was complete and concentrated to a thick oil. This oil was partitioned between EtOAc (3 mL) and water (2 mL) with stiffing for 10 minutes. The layers were then allowed to separate and the aqueous layer was discarded. The organic layer was then washed with water (2 mL), brine (2 ml) and dried over Na2SO4. Concentration gave an oil that was purified by column chromatography (30% EtOAc in hexanes) to give 6.1 mg (25% yield) of the desired isoxazole 6; 1H NMR (400 MHz, d6-DMSO) S 8.85 (d, 1H), 7.78 (d, 1H), 7.32 (t, 1H), 7.08 (s, 1H), 7.01 (d, 1H), 6.94 (t, 1H), 2.82 (m, 1H), 0.67 (m, 2H), 0.59 (m, 2H). LC/MS (electrospray ionization, positive mode) M+H=245.0.

1. waitAfter 2 hours
2. concentrationconcentrated to a thick oil
3. customThis oil was partitioned between EtOAc (3 mL) and water (2 mL)
4. waitwith stiffing for 10 minutes
5. customto separate
6. washThe organic layer was then washed with water (2 mL), brine (2 ml)
7. dry with materialdried over Na2SO4
8. concentrationConcentration
9. customgave an oil that
10. customwas purified by column chromatography (30% EtOAc in hexanes)

ORD record

ord-6c45c1ced734410c98753e22767209ac

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08778940B2