Triethylamine → HCID 86680043, compound

Temperature

0 °C

3-(2-Methyl-4-nitro-pyrazol-3-yl)-8-oxa-3-azabicyclo[3.2.1]octan-6-ol (500 mg, 1.96 mmoL) was dissolved in DCM (15 mL) and triethylamine (0.41 mL, 2.95 mmol) was added. After cooling to 0° C., methanesulfonyl chloride (0.19 mL, 2.45 mmol) was added slowly and the reaction mixture was allowed to warm to room temperature and stirred for 18 hr. The mixture was diluted with DCM (10 mL), quenched with water (10 mL) and the aqueous layer extracted with DCM (3×20 mL). The combined organic layers were washed with brine (10 mL), passed through a phase separation cartridge and concentrated under reduced pressure to give a light brown solid. This solid (450 mg, 1.35 mmol) was dissolved in DMF (20 mL), sodium azide (450 mg, 6.8 mmol) was added and the mixture heated at 150° C. for 18 hr, behind a blast shield. The mixture was allowed to cool to room temperature, the mixture partitioned between water (20 mL) and EtOAc (20 mL) and the aqueous layer extracted with EtOAc (3×25 mL). The combined organic layers were washed with brine (20 mL), dried over MgSO4 and concentrated under reduced pressure. Purification via silica gel column chromatography (10-50%, EtOAc/isohexane) gave 6-azido-3-(2-methyl-4-nitro-pyrazol-3-yl)-8-oxa-3-azabicyclo[3.2.1]octane as brown gum (25 mg, 68% over two steps). 1H NMR (400 MHz, CDCl3) δ 8.05 (s, 1H), 4.65 (d, J=7.4 Hz, 1H), 4.34 (s, 1H), 4.28 (dd, J=8.0, 3.2 Hz, 1H), 3.82 (s, 3H), 3.75-3.70 (m, 2H), 2.83-2.73 (m, 1H), 2.64-2.49 (m, 2H), 2.20 (ddd, J=13.4, 7.3, 3.2 Hz, 1H).

1. temperatureto warm to room temperature
2. customquenched with water (10 mL)
3. extractionthe aqueous layer extracted with DCM (3×20 mL)
4. washThe combined organic layers were washed with brine (10 mL)
5. custompassed through a phase separation cartridge
6. concentrationconcentrated under reduced pressure
7. customto give a light brown solid
8. temperaturethe mixture heated at 150° C. for 18 hr, behind a blast shield
9. temperatureto cool to room temperature
10. customthe mixture partitioned between water (20 mL) and EtOAc (20 mL)
11. extractionthe aqueous layer extracted with EtOAc (3×25 mL)
12. washThe combined organic layers were washed with brine (20 mL)
13. dry with materialdried over MgSO4
14. concentrationconcentrated under reduced pressure
15. customPurification via silica gel column chromatography (10-50%, EtOAc/isohexane)

ORD record

ord-67f2429dc9864d0b8f08f92b7d819ee4

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08614206B2