Lithium hydroxide, monohydrate → (S)-2-tert-butoxy-2-(1-(4-chlorophenyl)-3-methyl-6-(pyridin-4-yl)naphthalen-2-yl)acetic acid

HRID 514062Notes

Reaction equation

[C:1]([O:5][C@@H:6]([C:12]1[C:21]([CH3:22])=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:23]3[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=3)[CH:18]=2)[C:13]=1[C:29]1[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=1)[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].O[Li].O>C1COCC1.CO.O.CN(C=O)C>[C:1]([O:5][C@@H:6]([C:12]1[C:21]([CH3:22])=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:23]3[CH:24]=[CH:25][N:26]=[CH:27][CH:28]=3)[CH:18]=2)[C:13]=1[C:29]1[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 50 °C

Procedure

A solution (S)-ethyl 2-tert-butoxy-2-(1-(4-chlorophenyl)-3-methyl-6-(pyridin-4-yl)naphthalen-2-yl)acetate (0.043 g, 0.088 mmol) in THF/MeOH/H2O (1 mL each) was treated with LiOH.H2O (0.025 g, 0.59 mmol) and heated to 50° C. overnight. The resulting solution was diluted with DMF and purified by preparatory reverse phase HPLC (Gemini column, 15 to 100% MeCN/H2O, 0.1% TFA). Lyophilization of appropriate fractions afforded 0.021 g of 53 as an off-white amorphous powder. 1H-NMR: 400 MHz, (CD3CN) δ: 8.77 (br s, 2H); 8.37 (br s, 1H); 8.17 (br s, 2H); 7.91 (s, 1H); 7.76 (dd, J=8.8, 2.4 Hz, 1H); 7.62-7.54 (m, 3H); 7.46 (d, J=8.8 Hz, 1H); 7.38 (br d, J=8.8 Hz, 1H); 5.25 (s, 1H); 2.61 (s, 3H); 0.99 (s, 9H). LCMS-ESI− (m/z): [2M−H]− calcd for C56H51Cl2N2O6: 917.31; found: 917.51.

Workup

custompurified by preparatory reverse phase HPLC (Gemini column, 15 to 100% MeCN/H2O, 0.1% TFA)

Sources & evidence

ORD record: ord-0a9fbee78d004ec08cf0370565dc5399
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09102614B2

Reaction notes

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