Sodium hydride → 4-chloro-3-iodo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[3,2-c]pyridine
Reaction equation
[Cl:1][C:2]1[C:7]2[C:8]([I:11])=[CH:9][NH:10][C:6]=2[CH:5]=[CH:4][N:3]=1.[H-].[Na+].[CH3:14][Si:15]([CH3:22])([CH3:21])[CH2:16][CH2:17][O:18][CH2:19]Cl>CN(C)C=O.O1CCCC1.[Cl-].[Na+]>[Cl:1][C:2]1[C:7]2[C:8]([I:11])=[CH:9][N:10]([CH2:19][O:18][CH2:17][CH2:16][Si:15]([CH3:22])([CH3:21])[CH3:14])[C:6]=2[CH:5]=[CH:4][N:3]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 3
Procedure
To a 0° C. solution of C6 (900 mg, 3.2 mmol) in N,N-dimethylformamide (3 mL) and tetrahydrofuran (70 mL) was added sodium hydride (60% in mineral oil, 168 mg, 4.2 mmol). After 5 minutes, 2-(trimethylsilyl)ethoxymethyl chloride (592 mg, 3.55 mmol) was added to the cold mixture. The reaction mixture was stirred at room temperature for 3 hours, then cooled to 0° C. and treated with additional sodium hydride (56 mg, 1.4 mmol) and 2-(trimethylsilyl)ethoxymethyl chloride (197 mg, 1.18 mmol). After stirring at room temperature for 18 hours, the reaction mixture was diluted with saturated aqueous sodium chloride solution (100 mL) and extracted with ethyl acetate (2×100 mL). The combined organic layers were dried, filtered, and concentrated in vacuo. Silica gel chromatography (Gradient: 0% to 30% ethyl acetate in petroleum ether) provided the product as a yellow oil. Yield: 650 mg, 1.59 mmol, 50%. 1H NMR (400 MHz, CDCl3) δ 8.14 (d, J=6.0 Hz, 1H), 7.39 (d, J=6.0 Hz, 1H), 7.38 (s, 1H), 5.44 (s, 2H), 3.44-3.50 (m, 2H), 0.86-0.92 (m, 2H), −0.03 (s, 9H).
Workup
- temperaturecooled to 0° C.
- stirringAfter stirring at room temperature for 18 hours
- extractionextracted with ethyl acetate (2×100 mL)
- customThe combined organic layers were dried
- filtrationfiltered
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-e9a0823e85a04e1a8051429be3ebdbda
- Source dataset
- uspto-grants-2014_09
- Patent number
- US08822494B2
Reaction notes
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