Dimethylformamide → HCID 71305905, compound
Reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:18][CH2:17][C:11]2([CH:13]([C:14](O)=[O:15])[CH2:12]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[N:20](C)C=O.C(Cl)(=O)C(Cl)=O>C(Cl)Cl>[C:14]([CH:13]1[C:11]2([CH2:17][CH2:18][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]2)[CH2:12]1)(=[O:15])[NH2:20]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 15 °C
Procedure
To a mixture of 165d (400 mg, 1.57 mmol) and N,N-dimethylformamide (0.1 mL) in DCM (5 mL) was added oxalyl chloride (397 mg, 3.13 mmol) dropwise. See FIG. 6. The reaction mixture was stirred at 15° C. for 2.5 h and then concentrated. The residue was dissolved in tetrahydrofuran (20 mL) and added dropwise to aqueous ammonia (10 mL, 28%). The mixture was stirred at 15° C. for 4 h and then diluted with water (15 mL). The reaction mixture was extracted with EtOAc (15 mL×3). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated to afford tert-butyl 1-carbamoyl-6-azaspiro[2.5]octane-6-carboxylate 165e (260 mg, 65%) as a white solid. 1H NMR (400 MHz, CDCl3): δ 5.58 (s, 1H), 5.34 (s, 1H), 3.48-3.39 (m, 4H), 1.73-1.70 (m, 2H), 1.48 (s, 9H), 1.47-1.41 (m, 2H), 1.40-1.22 (m, 2H), 0.89-0.87 (m, 1H).
Workup
- concentrationconcentrated
- dissolutionThe residue was dissolved in tetrahydrofuran (20 mL)
- additionadded dropwise to aqueous ammonia (10 mL, 28%)
- stirringThe mixture was stirred at 15° C. for 4 h
- additiondiluted with water (15 mL)
- extractionThe reaction mixture was extracted with EtOAc (15 mL×3)
- dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-796ebf2780684c349bcaf5ee32944e1b
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09326985B2
Reaction notes
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