Methanol → 2-(5-Chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)acetic acid

HRID 913916Notes

Reaction equation

HRID 913916 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([CH2:11][C:12]#N)[C:8]2[C:4](=[CH:5][N:6]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[N:7]=2)[CH:3]=1.[OH-:22].[Na+].C[OH:25]>>[Cl:1][C:2]1[CH:10]=[C:9]([CH2:11][C:12]([OH:25])=[O:22])[C:8]2[C:4](=[CH:5][N:6]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[N:7]=2)[CH:3]=1

Participants

4

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 575459172-(5-Chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)acetonitrile

Product 1

HCID 575462532-(5-Chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)acetic acid

Procedure

To a solution of 2-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)acetonitrile (2.47 g, 7.25 mmol) in methanol (36 mL) was added sodium hydroxide (25% in water, 12 mL). The reaction was warmed to reflux and held there overnight. The reaction was cooled to room temperature, concentrated to remove the methanol. The resulting residue was diluted with diethyl ether (20 mL), cooled to 0° C., and made acidic by the cautious addition of concentrated hydrochloric acid with stirring. The resulting suspension was extracted with 1:1 diethyl ether/ethyl acetate (2×). The organics were washed with brine, dried over magnesium sulfate, and concentrated to give 2.47 g (100%) as an off white solid. 1H-NMR (CDCl3, 500 MHz) δ 9.98 (bs, 1H), 8.04 (s, 1H), 7.57 (d, J=1.5 Hz, 1H), 7.17 (d, J=0.9 Hz, 1H), 5.70 (s, 2), 4.04 (s, 2H), 3.61 (t, J=8.2 Hz, 2H), 0.91 (t, J=8.2 Hz, 2H), −0.05 (s, 9H), 13C NMR (126 MHz, CDCl3) δ ppm 174.5, 146.7, 128.4, 128.0, 125.1, 123.2, 122.5, 118.6, 81.9, 67.9, 36.9, 17.9, −1.4. Mass spec.: 341.11 (MH)+.

Workup

  1. temperatureThe reaction was warmed
  2. temperatureto reflux
  3. concentrationconcentrated
  4. customto remove the methanol
  5. additionThe resulting residue was diluted with diethyl ether (20 mL)
  6. temperaturecooled to 0° C.
  7. additionmade acidic by the cautious addition of concentrated hydrochloric acid
  8. extractionThe resulting suspension was extracted with 1:1 diethyl ether/ethyl acetate (2×)
  9. washThe organics were washed with brine
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated
  12. customto give 2.47 g (100%) as an off white solid

Sources & evidence

ORD record
ord-e36cd0aafcf347548fffc10897a3d840
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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