Lithium hydroxide, monohydrate → (R)-2-Hydroxy-3-(2-(methoxymethyl)-7-methyl-2H-indazol-5-yl)propanoic Acid

HRID 2099792Notes

Reaction equation

C([O:4][C@H:5]([CH2:10][C:11]1[CH:19]=[C:18]([CH3:20])[C:17]2[C:13](=[CH:14][N:15]([CH2:21][O:22][CH3:23])[N:16]=2)[CH:12]=1)[C:6]([O:8]C)=[O:7])(=O)C.O.[OH-].[Li+]>O1CCCC1.CO.O>[OH:4][C@H:5]([CH2:10][C:11]1[CH:19]=[C:18]([CH3:20])[C:17]2[C:13](=[CH:14][N:15]([CH2:21][O:22][CH3:23])[N:16]=2)[CH:12]=1)[C:6]([OH:8])=[O:7]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of (R)-methyl 2-acetoxy-3-(2-(methoxymethyl)-7-methyl-2H-indazol-5-yl)propanoate (2.70 g, 8.4 mmol) in tetrahydrofuran (20 mL) and methanol (20 mL) at 0° C. was added a solution of lithium hydroxide monohydrate (1.41 g, 4.0 equiv) in water (20 mL). The reaction was stirred at 0° C. for 1 h. The reaction was concentrated, dissolved in water (5 mL), cooled to 0° C., and treated with 1 M hydrochloric acid until mildly acidic. The solution was extracted extensively with ethyl acetate and then dichloromethane. The organics were combined, dried over magnesium sulfate, and concentrated to give 1.40 g (63%) as an oil which solidified to a crystalline solid upon standing. 1H-NMR (CDCl3, 500 MHz) δ 2.40 (s, 3H), 2.78 (dd, J=14.0, 7.9, 1H), 3.00 (dd, J=14.0, 4.0, 1H), 3.18 (s, 3H), 4.24 (dd, J=7.9, 4.3, 1H), 5.47 (s, 2H), 6.85 (s, 1H), 7.22 (s, 1H), 7.90 (s, 1H). Mass spec.: 265.08 (MH)+.

Workup

concentrationThe reaction was concentrated
dissolutiondissolved in water (5 mL)
temperaturecooled to 0° C.
additiontreated with 1 M hydrochloric acid until mildly acidic
extractionThe solution was extracted extensively with ethyl acetate
dry with materialdried over magnesium sulfate
concentrationconcentrated
customto give 1.40 g (63%) as an oil which

Sources & evidence

ORD record: ord-5a214152a96648eeadd04753ad54037d
Source dataset: uspto-grants-2009_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07569578B2

Reaction notes

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