Iodine → tert-Butyl 3-(hydroxymethyl)azetidine-1-carboxylate
Reaction equation
[BH4-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:13][CH:12]([C:14](O)=[O:15])[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].II.CO>C1COCC1>[OH:15][CH2:14][CH:12]1[CH2:13][N:10]([C:8]([O:7][C:3]([CH3:6])([CH3:5])[CH3:4])=[O:9])[CH2:11]1Participants
Procedure
To a stirred suspension of sodium borohydride (1.92 g, 50.6 mmol) in dry THF (20 mL) is added a solution of 1-(tert-butoxycarbonyl)azetidine-3-carboxylic acid in dry THF (20 mL) at 0° C. A solution of iodine (4.71 g, 18.6 mmol) in THF (20 mL) is added dropwise (caution: gas evolution) under N2 atmosphere. The reaction mixture is allowed to warm to room temperature then heated under reflux for 18 h. The resulting white suspension is cooled to room temperature. MeOH is added until the suspension dissolved. The mixture is concentrated under reduced pressure, then quenched with 1M aqueous KOH (100 mL) and extracted with DCM (3×150 mL). The organic phases are combined, washed with water followed by brine and concentrated under reduced pressure to give 2.13 g (27%) of tert-butyl 3-(hydroxymethyl)azetidine-1-carboxylate.
Workup
- temperaturethen heated
- temperatureunder reflux for 18 h
- temperatureThe resulting white suspension is cooled to room temperature
- dissolutiondissolved
- concentrationThe mixture is concentrated under reduced pressure
- customquenched with 1M aqueous KOH (100 mL)
- extractionextracted with DCM (3×150 mL)
- washwashed with water
- concentrationconcentrated under reduced pressure
Sources & evidence
- ORD record
- ord-aad6d9ff5a854c95b7d6d9ff545b38c0
- Source dataset
- uspto-grants-2013_12
- Patent number
- US08609696B2
Reaction notes
Loading…