Epichlorohydrin → 3-Benzyl-2-chloromethyl-[1,3]oxazepane
Reaction equation
[CH2:1]([NH:8][CH2:9][CH2:10][CH2:11]O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:13]([CH:15]1[O:17][CH2:16]1)[Cl:14]>>[CH2:1]([N:8]1[CH2:9][CH2:10][CH2:11][CH2:16][O:17][CH:15]1[CH2:13][Cl:14])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1Participants
Procedure
A solution of 3-benzylamino-propan-1-ol (14 g, 88.0 mmol) and epichlorohydrin (81.4 g, 880 mmol) was heated to 40° C. After stirring for 3 h the reaction was cooled and excess epichlorohydrin was removed by evaporation in vacuo. Sulfuric acid (10 mL) was added slowly, then the reaction flask was placed in a preheated oil bath at 150° C. Stirring proceeded for 1 h, then the reaction was allowed to cool to room temperature and quenched with the addition of ice. The mixture was adjusted to a basic pH with 10% aqueous Na2CO3 solution and extracted with EtOAc (3×300 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and dried under reduced pressure. The resulting residue was purified by flash chromatography (70:28:2 hexanes/CH2Cl2/2M NH4OH aq) to afford 5 g of a light yellow oil.
Workup
- temperaturewas cooled
- customexcess epichlorohydrin was removed by evaporation in vacuo
- additionSulfuric acid (10 mL) was added slowly
- customthe reaction flask was placed in a preheated oil bath at 150° C
- stirringStirring
- waitproceeded for 1 h
- customquenched with the addition of ice
- extractionextracted with EtOAc (3×300 mL)
- dry with materialThe combined organic layers were dried over anhydrous MgSO4
- filtrationfiltered
- customdried under reduced pressure
- customThe resulting residue was purified by flash chromatography (70:28:2 hexanes/CH2Cl2/2M NH4OH aq)
Sources & evidence
- ORD record
- ord-12d5b881d6f04219aaafb38bee184512
- Source dataset
- uspto-grants-2012_01
- Patent number
- US08093244B2
Reaction notes
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