Lithium Hydroxide → 4-(Methoxycarbonyl)bicyclo[2.2.2]octane-1-carboxylic acid

HRID 920856Notes

Reaction equation

[C:1]12([C:13]([O:15]C)=[O:14])[CH2:8][CH2:7][C:4]([C:9]([O:11][CH3:12])=[O:10])([CH2:5][CH2:6]1)[CH2:3][CH2:2]2.[Li+].[OH-]>CO.O>[CH3:12][O:11][C:9]([C:4]12[CH2:7][CH2:8][C:1]([C:13]([OH:15])=[O:14])([CH2:6][CH2:5]1)[CH2:2][CH2:3]2)=[O:10]

Participants

Conditions

Temperature: 65 °C

Procedure

To a solution of dimethyl bicyclo[2.2.2]octane-1,4-dicarboxylate (0.92 g, 4.07 mmol) in MeOH (5 mL) was added LiOH (0.102 g, 4.27 mmol) in water (4 mL) at RT. The reaction mixture was heated at 65° C. for 6 h. It was then cooled to RT and concentrated. The residue was acidified with 1N HCl to pH ˜2. The solid (presumed side product diacid) was removed by filtration. The filtrate was extracted with EtOAc, and the combined organic layer was washed with brine, dried over Na2SO4, and filtered. The filtrate was concentrated to afford Intermediate A51A as a white solid, which was used for the next step without further purification. MS(ES): m/z=213 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 12.11 (s, 1H), 3.66 (s, 3H), 1.78-1.58 (m, 1H).

Workup

temperatureIt was then cooled to RT
concentrationconcentrated
customThe solid (presumed side product diacid) was removed by filtration
extractionThe filtrate was extracted with EtOAc
washthe combined organic layer was washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationThe filtrate was concentrated
customto afford Intermediate A51A as a white solid, which
customwas used for the next step without further purification

Sources & evidence

ORD record: ord-7addf80c61f149029c308d912fc78629
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09273058B2

Reaction notes

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