Phosgene → Benzyl 4-(3,3-dimethylpiperidine-1-carbonyl)morpholine-2-carboxylate
Reaction equation
[C:1](Cl)(Cl)=[O:2].[NH:5]1[CH2:10][CH2:9][O:8][CH:7]([C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:12])[CH2:6]1.C(N(C(C)C)C(C)C)C.[CH3:30][C:31]1([CH3:37])[CH2:36][CH2:35][CH2:34][NH:33][CH2:32]1>C(Cl)Cl>[CH3:30][C:31]1([CH3:37])[CH2:36][CH2:35][CH2:34][N:33]([C:1]([N:5]2[CH2:10][CH2:9][O:8][CH:7]([C:11]([O:13][CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[O:12])[CH2:6]2)=[O:2])[CH2:32]1Participants
Conditions
- Temperature
- 0 °C
Procedure
In a dry 25-mL RBF, phosgene (0.25 ml, 0.47 mmol) was dissolved in DCM (2 mL) and the solution was cooled to 0° C. A solution of benzyl morpholine-2-carboxylate (50%, 0.070 g, 0.16 mmol, Example 458, Step 2) and N-ethyl-N-isopropylpropan-2-amine (0.041 ml, 0.24 mmol) in DCM (2 mL) was added. The solution was stirred at 0° C. for 4 h, and the ice bath was removed, and the mixture stirred at RT for 1 hour. The reaction mixture was concentrated, and the residue dissolved in DCM (2 mL), and N-ethyl-N -isopropylpropan-2-amine (0.041 ml, 0.24 mmol) and 3,3-dimethylpiperidine (0.022 g, 0.20 mmol) were added by syringe. After 14 h, the reaction mixture was concentrated. The residue was purified through silica gel (20 mL) using 50% EtOAc-hexane to afford the title compound. MS m/z 361 (M+1).
Workup
- customthe ice bath was removed
- stirringthe mixture stirred at RT for 1 hour
- concentrationThe reaction mixture was concentrated
- dissolutionthe residue dissolved in DCM (2 mL)
- waitAfter 14 h
- concentrationthe reaction mixture was concentrated
- customThe residue was purified through silica gel (20 mL)
Sources & evidence
- ORD record
- ord-54b563972a91413ab69b8cb895abe413
- Source dataset
- uspto-grants-2011_01
- Patent number
- US07872009B2
Reaction notes
Loading…