Methanol → (+/-)-2-Hydroxy-3-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)propanoic acid

HRID 501966Notes

Reaction equation

HRID 501966 reaction equation
C([O:9][C:10](=[CH:15][C:16]1[CH:24]=[C:23]([CH3:25])[C:22]2[C:18](=[CH:19][N:20]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[N:21]=2)[CH:17]=1)[C:11]([O:13]C)=[O:12])(=O)C1C=CC=CC=1.CO.[H][H].O.[OH-].[Li+]>O.[Pd]>[OH:9][CH:10]([CH2:15][C:16]1[CH:24]=[C:23]([CH3:25])[C:22]2[C:18](=[CH:19][N:20]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:32])([CH3:31])[CH3:33])[N:21]=2)[CH:17]=1)[C:11]([OH:13])=[O:12]

Participants

7

Reactant 4

HCID 887MethanolHCID 168937Lithium hydroxide, monohydrateHCID 684648731-methoxy-3-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)-1-oxoprop-2-en-2-yl benzoateHCID 178418361HCID 178418361, compound

Product 1

HCID 59424315(+/-)-2-Hydroxy-3-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)propanoic acid

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

A Parr bottle was charged with 1-methoxy-3-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)-1-oxoprop-2-en-2-yl benzoate (1.0 g, 2.14 mmol), methanol (15 mL), and palladium (10% on charcoal, 100 mg). The Parr shaker was pressurized to 60 psi of hydrogen and shaken for 6 h. The reaction was filtered through celite and concentrated. The resulting residue was dissolved in tetrahydrofuran (8 mL) and methanol (8 mL) and cooled to 0° C. To this was added a solution of lithium hydroxide monohydrate (358 mg, 8.54 mmol) in water (8 mL). The reaction was stirred at 0° C. for 1 h, then at room temperature for 2 h. The reaction was concentrated, dissovled in water, cooled to 0° C., and acidified with 1M hydrochloric acid. The resulting mixture was extracted with ethyl acetate (2×). The organics were washed with a minimum of brine, dried over magnesium sulfate, and concentrated. Column chromatography (5% to 10% methanol/dichloromethane) gave 340 mg (45%) as a colorless oil. 1H-NMR (CDCl3, 500 MHz) 8-0.04 (s, 9H), 0.93 (m, 2H), 2.53 (s, 3H), 2.92 (m, 1H), 3.19 (m, 1H), 3.61 (m, 2H), 4.46 (bs, 1H), 5.68 (s, 2H), 6.93 (s, 1H), 7.31 (bs, 1H), 7.94 (bs, 1H). Mass spec.: 351.36 (MH)+.

Workup

  1. filtrationThe reaction was filtered through celite and
  2. concentrationconcentrated
  3. dissolutionThe resulting residue was dissolved in tetrahydrofuran (8 mL)
  4. stirringThe reaction was stirred at 0° C. for 1 h
  5. waitat room temperature for 2 h
  6. concentrationThe reaction was concentrated
  7. temperaturecooled to 0° C.
  8. extractionThe resulting mixture was extracted with ethyl acetate (2×)
  9. washThe organics were washed with a minimum of brine
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated
  12. customColumn chromatography (5% to 10% methanol/dichloromethane) gave 340 mg (45%) as a colorless oil

Sources & evidence

ORD record
ord-0ca28cd4238b43a2855f734484beedc9
Source dataset
uspto-grants-2010_08
Patent number
US07772244B2

Reaction notes

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