Homoallyl bromide → HCID 58573986, compound
Reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]2[CH2:13][CH:12]([CH3:14])[C:11](=[O:15])[N:10]([C@@H:16]([CH2:26][CH3:27])[CH2:17][N:18]([CH3:25])[S:19]([CH:22]3[CH2:24][CH2:23]3)(=[O:21])=[O:20])[C@@H:9]2[C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=2)[CH:5]=[CH:6][CH:7]=1.C([N-]C(C)C)(C)C.[Li+].Br[CH2:44][CH2:45][CH:46]=[CH2:47]>C1COCC1>[CH2:44]([C:12]1([CH3:14])[CH2:13][C@H:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[C@@H:9]([C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=2)[N:10]([C@@H:16]([CH2:26][CH3:27])[CH2:17][N:18]([CH3:25])[S:19]([CH:22]2[CH2:23][CH2:24]2)(=[O:21])=[O:20])[C:11]1=[O:15])[CH2:45][CH:46]=[CH2:47]Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -15 °C
Procedure
To a solution of N-((2S)-2-((2S,3R)-3-(3-chlorophenyl)-2-(4-chlorophenyl)-5-methyl-6-oxopiperidin-1-yl)butyl)-N-methylcyclopropanesulfonamide (2618 mg, 5.0 mmol; Example 201, Step B) in degassed THF (10 mL) was added lithium diisopropylamide (5.00 mL, 10.00 mmol) at −15° C. After stirring at −15° C. for 30 min, the reaction mixture was cooled to −74° C. 4-Bromobut-1-ene (1.066 mL, 10.50 mmol) was added slowly. The reaction mixture was stirred at −74° C. for 3 h before warming up to rt and then stirred at rt for 66 h. Filtered and purified by HPLC (C18 column, eluted with 10 to 95% CH3CN in water, with 0.1% TFA) to give the title compound as the first eluting isomer Its stereoisomer is obtained as the later eluting isomer.
Workup
- temperaturethe reaction mixture was cooled to −74° C
- stirringThe reaction mixture was stirred at −74° C. for 3 h
- temperaturebefore warming up to rt
- stirringstirred at rt for 66 h
- filtrationFiltered
- custompurified by HPLC (C18 column, eluted with 10 to 95% CH3CN in water, with 0.1% TFA)
Sources & evidence
- ORD record
- ord-163dcee9221e4b4292a8b74191cfa62f
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09296736B2
Reaction notes
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