1-Bromo-3-chloropropane → 1-(3-Chloropropyl)azetidine-3-carbonitrile
Reaction equation
Cl.[NH:2]1[CH2:5][CH:4]([C:6]#[N:7])[CH2:3]1.Br[CH2:9][CH2:10][CH2:11][Cl:12].C([O-])([O-])=O.[Cs+].[Cs+]>C(#N)C.CCOC(C)=O>[Cl:12][CH2:11][CH2:10][CH2:9][N:2]1[CH2:5][CH:4]([C:6]#[N:7])[CH2:3]1Participants
Conditions
- Temperature
- 25 °C
Procedure
In a 25 mL round-bottomed flask were mixed with stirring azetidine-3-carbonitrile hydrochloride (available from ASW MedChem. Inc., 250 mg, 2.11 mmol) and 1-bromo-3-chloropropane (664 mg, 415 μL, 4.22 mmol.0) in acetonitrile (5 mL) to the suspension was added Cs2CO3 (2.06 g, 6.33 mmol). The mixture was stirred at 25° C. for 18 h, then diluted with 15 mL of EtOAc and filtered to remove solids. Filtrate was evaporated and residue purified by chromatography (40 g column, 50 μm from Analogix, 0 to 5% over 20 min (MeOH containing 10% ammonium hydroxide)/dichloromethane (developing TLC in an iodine chamber) to give 1-(3-chloropropyl)azetidine-3-carbonitrile (230 mg, 1.45 mmol, 68.8%) as a clear dense liquid. 1H NMR (CDCl3) δ: 3.46-3.59 (m, 4H), 3.20-3.31 (m, 3H), 2.55 (t, J=6.8 Hz, 2H), 1.75 (quin, J=6.6 Hz, 2H).
Workup
- filtrationfiltered
- customto remove solids
- customFiltrate was evaporated
- customresidue purified by chromatography (40 g column, 50 μm from Analogix, 0 to 5% over 20 min (MeOH containing 10% ammonium hydroxide)/dichloromethane (
Sources & evidence
- ORD record
- ord-df3947187c67401cbaea42473ad86ad8
- Source dataset
- uspto-grants-2014_02
- Patent number
- US08658646B2
Reaction notes
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