Reaction equation
[C@@H:1]12[CH2:7][C@@H:4]([CH2:5][CH2:6]1)[CH2:3][C@@H:2]2[NH:8][C:9]1[S:10][CH:11]([CH2:15][CH2:16][O:17][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)[C:12](=[O:14])[N:13]=1.[Li+].CC([N-]C(C)C)C.Br[CH2:33][C:34]([CH3:36])=[CH2:35]>C1COCC1>[C@@H:1]12[CH2:7][C@@H:4]([CH2:5][CH2:6]1)[CH2:3][C@@H:2]2[NH:8][C:9]1[S:10][C:11]([CH2:35][C:34]([CH3:36])=[CH2:33])([CH2:15][CH2:16][O:17][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)[C:12](=[O:14])[N:13]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -78 °C
Procedure
To the mixture of 2-((1S,2S,4R)-bicyclo[2.2.1]heptan-2-ylamino)-5-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)thiazol-4(5H)-one (1160 mg, 3.43 mmol) in THF (8.0 mL) cooled in a −78° C. bath was added LDA (2.0 M, 17.15 mL). The resulting mixture was stirred for 10 min at −78° C., and then 3-bromo-2-methylprop-1-ene (1.6 ml, 17.15 mmol) was added. After the reaction mixture was allowed to warm to room temperature and stirred ca. 18 h. Saturated NaH2PO4 was added, and the aqueous phase was extracted with EtOAc. The organic layer was washed with sat'd NH4Cl, dried over MgSO4, filtered, and concentrated in vacuo. The crude residue was purified by flash chromatography (4:1; Hexane:EtOAc) to give the title compound as yellow oil. MS (ES+): 393 (M+H)+.
Workup
- temperatureto warm to room temperature
- stirringstirred ca. 18 h
- extractionthe aqueous phase was extracted with EtOAc
- washThe organic layer was washed with sat'd NH4Cl
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe crude residue was purified by flash chromatography (4:1; Hexane:EtOAc)
Sources & evidence
- ORD record
- ord-b7dd2c3c2757432280f485cab6696c81
- Source dataset
- uspto-grants-2014_04
- Patent number
- US08686011B2
Linked notes
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