Dimethylformamide → 4-(4-Bromo-thiazol-2-yl)-cis-2,6-dimethyl-morpholine
Reaction equation
Br[C:2]1[S:3][CH:4]=[C:5]([Br:7])[N:6]=1.CN(C=O)C.[CH3:13][C@H:14]1[O:19][C@@H:18]([CH3:20])[CH2:17][NH:16][CH2:15]1.CCN(C(C)C)C(C)C>O>[Br:7][C:5]1[N:6]=[C:2]([N:16]2[CH2:15][C@H:14]([CH3:13])[O:19][C@H:18]([CH3:20])[CH2:17]2)[S:3][CH:4]=1Participants
Conditions
- Temperature
- 70 °C
Procedure
A 1 L flask equipped with a mechanical stirrer and a thermometer was charged with 2,4-dibromothiazole (60 g, 0.247 mol) and DMF (480 mL). After dissolution, cis-2,6-dimethylmorpholine (33.65 mL, 0.272 mol) and DIPEA (61.23 mL, 0.37 mol) were added under a stream of nitrogen. The reaction mixture was heated to 70° C. under nitrogen and stirred overnight. The reaction mixture was cooled to 10° C. in an ice/water bath. Then water (1 L) was added dropwise in a temperature range of 10-20° C. A slightly exothermic reaction was observed, with formation of an off-white precipitate. After the addition, the reaction mixture was stirred for 30 min. The precipitate was then filtered and washed with water (50 ml). The collected solid was dried in a vacuum oven at 50° C., yielding 52.8 g (77%) of Intermediate 1 as an off-white solid.
Workup
- customA 1 L flask equipped with a mechanical stirrer
- additionwere added under a stream of nitrogen
- temperatureThe reaction mixture was cooled to 10° C. in an ice/water bath
- customA slightly exothermic reaction
- additionAfter the addition
- stirringthe reaction mixture was stirred for 30 min
- filtrationThe precipitate was then filtered
- washwashed with water (50 ml)
- customThe collected solid was dried in a vacuum oven at 50° C.
Sources & evidence
- ORD record
- ord-b5e12114e872470793a8a0ceba490bab
- Source dataset
- uspto-grants-2014_01
- Patent number
- US08637510B2
Reaction notes
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