Ethanol → 2-Tert-butoxy-2-(1-(4-chlorophenyl)-4-(hydroxymethyl)-3-methylnaphthalen-2-yl)acetic acid

HRID 514132Notes

Reaction equation

[C:1]([O:5][CH:6]([C:12]1[C:21]([CH3:22])=[C:20]([CH:23]=[O:24])[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]=1[C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=1)[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+].C1COCC1.CCO>O>[C:1]([O:5][CH:6]([C:12]1[C:21]([CH3:22])=[C:20]([CH2:23][OH:24])[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]=1[C:25]1[CH:26]=[CH:27][C:28]([Cl:31])=[CH:29][CH:30]=1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 100 °C

Procedure

A solution of ethyl 2-tert-butoxy-2-(1-(4-chlorophenyl)-4-formyl-3-methylnaphthalen-2-yl)acetate (6.0 mg, 14 μmol), NaBH4 (1.5 mg, 40 μmol), THF (250 μL), and EtOH (absolute, 500 μL) was stirred at 23° C. for 1 h. H2O (500 μL) and LiOH monohydrate (50 mg, 1.18 mmol) were added. The reaction was sealed and heated to 100° C. After 2 h, the reaction 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) (2.6 mg, 43%). 1H NMR (400 MHz, DMSO-d6) δ 12.76 (s, 1H), 8.27 (d, J=8.6 Hz, 1H), 7.72-7.65 (m, 2H), 7.58-7.48 (m, 2H), 7.39-7.33 (m, 2H), 7.18 (d, J=8.6 Hz, 1H), 5.07 (s, 1H), 5.01 (d, broad, J=2.7 Hz, 2H), 2.62 (s, 3H), 0.94 (s, 9H).

Workup

customThe reaction was sealed
temperaturethe reaction 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-45566da7593a473fbc16c1712b2d1b48
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09102614B2

Reaction notes

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