Lithium Hydroxide → 6-(2,2-difluoroethoxy)nicotinic acid

Reaction equation

Cl[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8]CC)=[O:7])=[CH:4][N:3]=1.[F:13][C:14](F)([F:17])[CH2:15][OH:16].[OH-].[Li+]>>[F:13][CH:14]([F:17])[CH2:15][O:16][C:2]1[CH:12]=[CH:11][C:5]([C:6]([OH:8])=[O:7])=[CH:4][N:3]=1

Participants

Reactant 3

HCID 3939Lithium Hydroxide

HCID 64092,2,2-Trifluoroethanol

HCID 2799611Ethyl 6-chloronicotinate

Product 1

HCID 251162916-(2,2-difluoroethoxy)nicotinic acidYield 79%

Procedure

The title compound was synthesized as described for Intermediate example I-81 in 79% yield starting from ethyl 6-chloronicotinate and 2,2,2-trifluoroethanol. The reduction was performed using 3 equiv of lithium hydroxide, the reaction mixture was stirred at ambient temperature over night; 1H NMR (400 MHz, DMSO-d6) δ ppm 8.73 (d, 1 H), 8.20 (dd, 1 H), 7.02 (d, 1 H), 6.21-6.57 (m, 1 H), 4.65 (dt, 2 H); MS (ESI) m/z 202[M−H+].

Sources & evidence

ORD record: ord-94c1095970ab4d14806e86debf36c7d8
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08143408B2

Reaction notes

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