2-Chloromethyl 2-(trimethylsilyl)ethyl ether → 3-Chloro-5-(1,3-dioxan-2-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-indazole

HRID 1038399Notes

Reaction equation

[Cl:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH:11]3[O:16][CH2:15][CH2:14][CH2:13][O:12]3)[CH:9]=2)[NH:4][N:3]=1.CC(C)([O-])C.[Na+].[CH3:23][Si:24]([CH3:31])([CH3:30])[CH2:25][CH2:26][O:27][CH2:28]Cl>C1COCC1>[Cl:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH:11]3[O:16][CH2:15][CH2:14][CH2:13][O:12]3)[CH:9]=2)[N:4]([CH2:28][O:27][CH2:26][CH2:25][Si:24]([CH3:31])([CH3:30])[CH3:23])[N:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 2.7 g (11.3 mmol) 3-chloro-5-(1,3-dioxan-2-yl)-1H-indazole (Example 44A) in anhydrous THF (60 ml) were added 1.31 g (13.6 mmol) sodium tert-butoxide at room temperature. The solution was cooled to 0° C., and 2.26 g (13.6 mmol) 2-(trimethylsilyl)ethoxymethyl chloride were added at this temperature. The resulting mixture was stirred at 0° C. for 1 h and then concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed with water and with brine. The organic layer was dried with sodium sulfate, filtered and evaporated to dryness. The residue was purified by flash chromatography (silica gel; cyclohexane/ethyl acetate 5:1 v/v) to give 1.73 g (41% of th.) of the title compound.

Workup

concentrationconcentrated under reduced pressure
dissolutionThe residue was dissolved in ethyl acetate
washwashed with water and with brine
dry with materialThe organic layer was dried with sodium sulfate
filtrationfiltered
customevaporated to dryness
customThe residue was purified by flash chromatography (silica gel; cyclohexane/ethyl acetate 5:1 v/v)

Sources & evidence

ORD record: ord-a6d8d1eefdf74af5a4b1c6a65d6bc164
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08551989B2

Reaction notes

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