5-Bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-7-carbaldehyde → (+/-)-1-(5-Bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-7-yl)ethanol
Reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH:11]=[O:12])[CH:10]=1)[N:7]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[N:6]=[CH:5]2.[CH3:21][Mg]Br>O1CCCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH:11]([OH:12])[CH3:21])[CH:10]=1)[N:7]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[N:6]=[CH:5]2Participants
Conditions
- Temperature
- 0 °C
Procedure
To a solution of 5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-7-carbaldehyde (600 mg, 1.689 mmol) in tetrahydrofuran (10 mL) at −78° C. was added methylmagnesiumbromide (3M in diethyl ether, 1.13 mL, 3.38 mmol). After 5 min, the ice bath was removed and stirring continued for 30 min. The reaction was cooled to 0° C. and quenched by the cautious addition of saturated ammonium chloride. The mixture was poured into diethyl ether, washed with water (2×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (12%→25% EtOAc/Hex) gave 575 mg (92%) as a colorless oil. 1H-NMR (CDCl3, 500 MHz) δ 7.89 (s, 1H), 7.76 (s, 1H), 7.61 (s, 1H), 5.92 (d, J=11.6, 1H), 5.80 (d, J=11.6, 1H), 5.56 (m, 1H), 3.46 (m, 2H), 3.26 (s, 1H), 1.64 (d, J=6.4, 3H), 0.80 (m, 2H), −0.11 (s, 9H); 13C NMR (126 MHz, CDCl3) δ ppm 136.2, 133.5, 130.8, 128.1, 126.9, 122.9, 114.8, 80.3, 66.5, 64.6, 23.0, 17.8, −1.4.
Workup
- customthe ice bath was removed
- waitcontinued for 30 min
- customquenched by the cautious addition of saturated ammonium chloride
- additionThe mixture was poured into diethyl ether
- washwashed with water (2×)
- dry with materialbrine, dried over magnesium sulfate
- concentrationconcentrated
- customColumn chromatography (12%→25% EtOAc/Hex) gave 575 mg (92%) as a colorless oil
Sources & evidence
- ORD record
- ord-118fac5e9227461498b6e3bdc2ffe57a
- Source dataset
- uspto-grants-2011_09
- Patent number
- US08026257B2
Reaction notes
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