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

HRID 501938Notes

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 1M hydrochloric acid until mildly acidic. The solution was 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 1M hydrochloric acid until mildly acidic
extractionThe solution was 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-f032a5a578a94ef0b3eee6446bf6e22c
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07772244B2

Reaction notes

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