Diisopropylamine → 8-(Phenylmethyl)-3-oxa-1,8-diazaspiro[4.5]decan-2-one
Reaction equation
[NH2:1][C:2]1([CH2:15][OH:16])[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.C(NC(C)C)(C)C.Cl[C:25](Cl)([O:27]C(=O)OC(Cl)(Cl)Cl)Cl.[NH4+].[OH-]>C1(C)C=CC=CC=1.O>[CH2:8]([N:5]1[CH2:6][CH2:7][C:2]2([NH:1][C:25](=[O:27])[O:16][CH2:15]2)[CH2:3][CH2:4]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1Participants
Conditions
- Temperature
- 0 °C
Procedure
To a 1 L 4-neck round bottom flask was added (4-amino-1-benzylpiperidin-4-yl)methanol (21.86 g, 99 mmol) and diisopropyl amine (23.0 g, 249 mmol) in dry toluene (300 ml). The reaction mixture was cooled to 0° C. and a solution of triphosgene (35.57 g, 119 mmol) in toluene (100 ml) was added. The reaction mixture was heated to 60° C. for 1.5 h. After cooling to room temperature, the reaction mixture was diluted with water (200 ml), basified with aqueous NH4OH, and extracted with ethyl acetate (3×200 ml). The organic layers were combined and washed with two 200 ml portions of water and 200 ml of brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The solid was stirred in hexanes for 1.5 hours and filtered again to afford the title compound.
Workup
- temperatureThe reaction mixture was heated to 60° C. for 1.5 h
- temperatureAfter cooling to room temperature
- extractionextracted with ethyl acetate (3×200 ml)
- washwashed with two 200 ml portions of water and 200 ml of brine
- dry with materialdried over anhydrous sodium sulfate
- filtrationfiltered
- concentrationconcentrated
- filtrationfiltered again
Sources & evidence
- ORD record
- ord-320ca4f908cc474bae0d74b4ba3de81e
- Source dataset
- uspto-grants-2013_02
- Patent number
- US08367706B2
Reaction notes
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