Thionyl Chloride → Benzyl 3-[(4-cyclobutylpiperazin-1-yl)carbonyl]azetidine-1-carboxylate
Reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:14][CH:13]([C:15]([OH:17])=O)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O=S(Cl)Cl.[CH:22]1([N:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)[CH2:25][CH2:24][CH2:23]1.CCN(C(C)C)C(C)C>ClCCl>[CH:22]1([N:26]2[CH2:31][CH2:30][N:29]([C:15]([CH:13]3[CH2:12][N:11]([C:9]([O:8][CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)=[O:10])[CH2:14]3)=[O:17])[CH2:28][CH2:27]2)[CH2:25][CH2:24][CH2:23]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
To a stirred solution of 1-[(benzyloxy)carbonyl]azetidine-3-carboxylic acid (250 mg, 1.06 mmol) in dichloromethane (2 mL) at RT was added SOCl2 (115 μL, 1.59 mmol). The mixture was stirred for 18 hours before volatiles were removed at reduced pressure. The residue was then dissolved in dichlormethane (3 mL) and 1-cyclobutylpiperazine (115 mg, 1.28 mmol) followed by DIPEA (940 μL, 5.31 mmol) added. The mixture was stirred at RT for 4 hours and then quenched with saturated aq. NaHCO3 (1 mL). The aqueous phase was extracted with dichloromethane (2×5 mL), the organics combined, washed with brine (2 mL), dried (MgSO4), filtered and concentrated at reduced pressure to give the title compound (130 mg, 34%), after purification by silica FCC (97.5:2.25:0.25 DCM/MeOH/NH3).
Workup
- customwere removed at reduced pressure
- dissolutionThe residue was then dissolved in dichlormethane (3 mL)
- additionadded
- stirringThe mixture was stirred at RT for 4 hours
- customquenched with saturated aq. NaHCO3 (1 mL)
- extractionThe aqueous phase was extracted with dichloromethane (2×5 mL)
- washwashed with brine (2 mL)
- dry with materialdried (MgSO4)
- filtrationfiltered
- concentrationconcentrated at reduced pressure
Sources & evidence
- ORD record
- ord-2ce4e4b7992143718ac9f42304cd78aa
- Source dataset
- uspto-grants-2014_12
- Patent number
- US08912176B2
Reaction notes
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