Triethylamine → 2-[3-(2-azidoethyl)-6-fluoro-1H-indol-2-yl]-propanedioic acid dimethyl ester
Reaction equation
[N:1]([CH2:4][CH2:5][C:6]1[C:14]2[C:9](=[CH:10][C:11]([F:15])=[CH:12][CH:13]=2)[NH:8][CH:7]=1)=[N+:2]=[N-:3].CCN(CC)CC.C(OCl)(C)(C)C.[Li][CH:30]([C:35]([O:37][CH3:38])=[O:36])[C:31]([O:33][CH3:34])=[O:32]>C1COCC1.CCOCC.O.[Cl-].[Cl-].[Zn+2]>[CH3:34][O:33][C:31](=[O:32])[CH:30]([C:7]1[NH:8][C:9]2[C:14]([C:6]=1[CH2:5][CH2:4][N:1]=[N+:2]=[N-:3])=[CH:13][CH:12]=[C:11]([F:15])[CH:10]=2)[C:35]([O:37][CH3:38])=[O:36]Participants
9
Reactant 4
Product 1
Reagents, catalysts & solvents 4
Conditions
- Temperature
- -78 °C
Procedure
To a solution of 3-(2-azidoethyl)-6-fluoro-1H-indole (4.77 g, 23.3 mmol) and NEt3 (3.63 mL, 25.8 mmol) in dry THF (0.13 L) at −78° C. under argon was added tBuOCl (3.04 mL, 26.9 mmol). The reaction mixture was stirred for 30 min at −78° C. A solution of 1 M ZnCl2 in Et2O (5.0 mL) was added. After 15 min a solution of dimethyl lithiomalonate (28.1 mmol in THF/hexanes) was added. The mixture was stirred at −78° C. for 1 h and at rt overnight, diluted with cold water, then extracted with Et2O. The Et2O extracts were dried, filtered, and concentrated to give the title compound: TLC Rf=0.46 (CH2Cl2); MS (ESI−) m/z 333.1; 1H NMR (CDCl3, 300 MHz) δ 8.97 (1H), 7.45 (1H), 7.05 (1H), 6.89 (1H), 5.02 (1H), 3.80 (6H), 3.50 (2H), 2.97 (2H).
Workup
- stirringThe mixture was stirred at −78° C. for 1 h and at rt overnight
- extractionextracted with Et2O
- dry with materialThe Et2O extracts were dried
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-a09d2424d1a14aa395bcb6878f9d2c2b
- Source dataset
- uspto-grants-2005_06
- Patent number
- US06903090B2
Reaction notes
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