Water → 2-Tert-butoxy-2-(1-(4-chlorophenyl)-3,4-dimethylnaphthalen-2-yl)acetic acid

HRID 514124Notes

Reaction equation

[C:1]([O:5][CH:6]([C:12]1[C:21]([CH3:22])=[C:20]([CH3:23])[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]=1[C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=1)[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].O>C1COCC1.CCO>[C:1]([O:5][CH:6]([C:12]1[C:21]([CH3:22])=[C:20]([CH3:23])[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]=1[C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 100 °C

Procedure

A solution of the crude ethyl 2-tert-butoxy-2-(1-(4-chlorophenyl)-3,4-dimethylnaphthalen-2-yl)acetate in THF (500 μL), EtOH (Absolute, 250 μL), and H2O (250 μL) was treated with LiOH monohydrate (61 mg, 1.45 mmol) and heated to 100° C. in a sealed vessel for 4 h. The reaction was cooled to 23° C., filtered through a 0.45 micron filter, and directly purified by reverse phase HPLC (Gemini, 5 to 100% ACN/H2O+0.1% TFA). The product-containing fractions were combined and lyophilized, giving the title compound (parent form) (8.0 mg, 40% over 2 steps). 1H NMR (400 MHz, DMSO-d6) δ 12.73 (s, broad, 1H), 8.15 (d, J=8.2 Hz, 1H), 7.72-7.62 (m, 2H), 7.57-7.47 (m, 2H), 7.39-7.32 (m, 2H), 7.19 (d, J=8.2 Hz, 1H), 5.07 (s, 1H), 2.63 (s, 3H), 2.51 (s, 3H), 0.93 (s, 9H).

Workup

temperatureThe reaction was cooled to 23° C.
filtrationfiltered through a 0.45 micron
filtrationfilter
customdirectly purified by reverse phase HPLC (Gemini, 5 to 100% ACN/H2O+0.1% TFA)

Sources & evidence

ORD record: ord-dbe64776b1204105a186b3f93ed2971d
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09102614B2

Reaction notes

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