Tricyclo(3.3.1.1'3,7)dec-1-ylmethanol → 6-(Adamantan-1-ylmethoxy)-5-chloronicotinic acid

HRID 1849578Notes

Reaction equation

[C:1]12([CH2:11][OH:12])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[Cl:13][C:14]1[C:15](Cl)=[N:16][CH:17]=[C:18]([CH:22]=1)[C:19]([OH:21])=[O:20].CC(C)([O-])C.[K+]>CS(C)=O.C(OCC)(=O)C.Cl>[C:1]12([CH2:11][O:12][C:15]3[C:14]([Cl:13])=[CH:22][C:18]([C:19]([OH:21])=[O:20])=[CH:17][N:16]=3)[CH2:8][CH:7]3[CH2:6][CH:5]([CH2:4][CH:3]([CH2:9]3)[CH2:2]1)[CH2:10]2

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 1-adamantylmethanol (5.32 g, 32.00 mmol), 5,6-dichloronicotinic acid (6.14 g, 32.00 mmol) and potassium tert-butoxide (8.3 g, 73.60 mmol) in anhydrous dimethyl sulfoxide (100 mL) was heated to 80° C. under nitrogen for 1 h. The reaction mixture was cooled to ambient temperature and diluted with ethyl acetate (500 mL) and 1.0 M aqueous hydrochloric acid (300 mL). The layers were separated and the organic layer was washed with 1.0 M aqueous hydrochloric acid (100 mL), brine (2×100 mL); dried over anhydrous sodium sulfate; filtered and concentrated in vacuo. The residue was triturated with diethyl ether to afford the title compound as a white solid (4.32 g, 42%); 1H NMR (300 MHz, DMSO-d6) δ 13.23 (br s, 1H), 8.56 (d, J=2.0 Hz, 1H), 8.14 (d, J=2.0 Hz, 1H), 3.95 (s, 1H), 2.00-1.88 (m, 3H), 1.71-1.50 (m, 12H); MS (ES−) m/z: 320.3, 322.3 (M−1).

Workup

temperatureThe reaction mixture was cooled to ambient temperature
customThe layers were separated
washthe organic layer was washed with 1.0 M aqueous hydrochloric acid (100 mL), brine (2×100 mL)
dry with materialdried over anhydrous sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was triturated with diethyl ether

Sources & evidence

ORD record: ord-6cc25cccbe7a439a8dad25771efd10ec
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08952169B2

Reaction notes

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