Sulfuric Acid → (S)-2-Hydroxymethyl-azetidine-1-carboxylic acid benzyl ester
Reaction equation
[NH:1]1[CH2:4][CH2:3][C@H:2]1[CH2:5][OH:6].S(=O)(=O)(O)O.C(=O)([O-])O.[Na+].[CH2:17]([O:24][C:25](Cl)=[O:26])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[CH2:17]([O:24][C:25]([N:1]1[CH2:4][CH2:3][C@H:2]1[CH2:5][OH:6])=[O:26])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1Participants
Procedure
This solution of (S)-azetidine-2-methanol was adjusted to pH 10 by adding 10% sulfuric acid, sodium hydrogen carbonate (2.00 g, 24.0 mmol) was then added, and benzyloxycarbonyl chloride (4.00 g, 24.0 mmol) was added thereto at room temperature. The mixture was then stirred for 14 hours. The solution was adjusted to pH 7, and extracted with ethyl acetate (50 mL×2). The extract was washed with water (50 mL×1), dried over magnesium sulfate and filtered, and the filtrate was concentrated. The concentrate was subjected to column chromatography (Wakogel C-200) using toluene/ethyl acetate (1/1) as a mobile phase. This separation/purification gave (S)-N-benzyloxycarbonylazetidine-2-methanol (1.88 g, yield 85.0%). The yield was improved as compared with that obtained in Example 1 (69.1%). The formation of the byproduct (S)-2-N-benzyloxycarbonyl-1,4-butanediol decreased to a yield of 3.0% (0.07 g).
Workup
- additionwas then added
- customat room temperature
- extractionextracted with ethyl acetate (50 mL×2)
- washThe extract was washed with water (50 mL×1)
- dry with materialdried over magnesium sulfate
- filtrationfiltered
- concentrationthe filtrate was concentrated
- customThis separation/purification
Sources & evidence
- ORD record
- ord-3a5df932c75c4c50a62a2819e94b6d07
- Source dataset
- uspto-grants-2000_11
- Patent number
- US06150535
Reaction notes
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