Lithium diisopropylamide → tert-Butyl 4-[2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-oxoethyl]-3-oxopiperazine-1-carboxylate
Reaction equation
[O:1]=[C:2]1[NH:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.[Li+].CC([N-]C(C)C)C.Br[CH2:24][C:25]([C:27]1[CH:36]=[CH:35][C:30]2[C:31](=[O:34])[O:32][CH2:33][C:29]=2[C:28]=1[CH3:37])=[O:26]>C1COCC1>[CH3:37][C:28]1[C:29]2[CH2:33][O:32][C:31](=[O:34])[C:30]=2[CH:35]=[CH:36][C:27]=1[C:25](=[O:26])[CH2:24][N:7]1[CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3][C:2]1=[O:1]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To a THF solution of tert-Butyl 3-oxopiperazine-1-carboxylate (164 mg, 0.82 mmol) was dropped LDA (0.37 ml, 0.74 mmol) at −78° C. After stirring the solution for 15 minutes, a THF solution of 5-(bromoacetyl)-4-methyl-2-benzofuran-1(3H)-one (200 mg, 0.74 mmol) was added into the reaction. TLC showed formation of a new spot right away. LC confirmed the desired alkylation product. The product was purified by MPLC to afford tert-Butyl 4-[2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-oxoethyl]-3-oxopiperazine-1-carboxylate. LC-MS (IE, m/z): 389 [M+1]+. The resulting solid was further treated with TFA to remove the BOC group. The crude material was dissolved in aqueous sodium bicarbonate, extracted with Chloroform-IPA (3:1) three times, dried over sodium sulfate, and concentrated to furnish the free base of 1-[2-(4-Methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-oxoethyl]piperazin-2-one.
Workup
- customThe product was purified by MPLC
Sources & evidence
- ORD record
- ord-403820dd10124547aca9428d2d855bb8
- Source dataset
- uspto-grants-2015_04
- Patent number
- US08999990B2
Reaction notes
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