Dimethylformamide → N-methoxy-N-methyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-2-carboxamide

Temperature

5.5 °C

To a cooled (5-6° C.), stirred suspension of crude potassium 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-2-carboxylate (21.9 g, 115 mmol) in dichloromethane (180 mL) containing N,N-dimethylformamide (2.5 mL, 32.3 mmol), is added, dropwise, oxalyl chloride (19.0 mL, 218 mmol) over a period of 10 minutes. The reaction is exothermic with gas evolution. After the addition, the ice-bath is removed and the reaction mixture stirred at room temperature. After 5 hours, the solution is added to a cooled, stirred (10-12° C.) suspension of N,O-dimethylhydroxylamine hydrochloride (17.6 g, 180 mmol) in dichloromethane (80 mL) containing N,N-diisopropylethyamine (100 mL, 574 mmol). After 18 hours at room temperature, water (150 mL) is added. The two layers are separated. The organic layer is extracted with water (3×150 mL), and the organic layer dried over anhydrous sodium sulfate, filtered and concentrated under diminished pressure to give a brown solid which is recrystallized from ether (35 mL) to give 15.6 g (69%) of N-methoxy-N-methyl-5,6-dihydro-4H-pyrrolo[1,2-b]-pyrazole-2-carboxamide as a brown solid having HPLC purity, 91.3% (HPLC conditions described in Example 17).

1. additionis added
2. additionAfter the addition
3. customthe ice-bath is removed
4. stirringthe reaction mixture stirred at room temperature
5. additionthe solution is added to a cooled
6. stirringstirred
7. waitAfter 18 hours at room temperature
8. customThe two layers are separated
9. extractionThe organic layer is extracted with water (3×150 mL)
10. dry with materialthe organic layer dried over anhydrous sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated under diminished pressure
13. customto give a brown solid which
14. customis recrystallized from ether (35 mL)

ORD record

ord-07d8eb95f8f440d49edfa421b09b5d09

Source dataset

uspto-grants-2007_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07276611B2