Lithium hydroxide, monohydrate → HCID 71603267, compound

HRID 2363886Notes

Reaction equation

HRID 2363886 reaction equation
C[O:2][C:3](=[O:34])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([CH:16]2[CH2:21][CH2:20][N:19]([C:22](=[O:32])[NH:23][C:24]3[C:29]([F:30])=[CH:28][CH:27]=[CH:26][C:25]=3[F:31])[CH2:18][CH2:17]2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:33])[CH:11]=2)[CH:6]=1.O.[OH-].[Li+]>C1COCC1.O>[F:31][C:25]1[CH:26]=[CH:27][CH:28]=[C:29]([F:30])[C:24]=1[NH:23][C:22]([N:19]1[CH2:20][CH2:21][CH:16]([C:13]2[C:12]3[C:7](=[CH:8][CH:9]=[C:10]([F:33])[CH:11]=3)[CH:6]=[C:5]([CH2:4][C:3]([OH:34])=[O:2])[C:14]=2[CH3:15])[CH2:17][CH2:18]1)=[O:32]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86686923HCID 86686923, compound

Product 1

HCID 71603267HCID 71603267, compoundYield 64%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of {4-[1-(2,6-difluoro-phenylcarbamoyl)-piperidin-4-yl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid methyl ester (95.4 mg, 0.203 mmol) in THF (8.0 mL) was added a solution of lithium hydroxide monohydrate (97.2 mg, 2.3 mmol) in water (2.0 mL) at room temperature. The resulting solution was stirred overnight at room temperature under a nitrogen atmosphere. Then, the solvent was removed and the residue was combined with water (25 mL). The mixture was neutralized with 1.0 N HCl. The resulting white precipitate was collected by filtration and dried under high vacuum to provide {4-[1-(2,6-difluoro-phenyl-carbamoyl)-piperidin-4-yl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid (59.2 mg, 64%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.46 (br. s, 1H), 8.38 (br. s, 1H), 7.90 (dd, J=9.00, 6.40 Hz, 1H), 7.75-7.85 (m, 1H), 7.65-7.74 (m, 1H), 7.24-7.42 (m, 2H), 7.14 (m, 2H), 4.17-4.38 (m, 2H), 3.79 (m, 3H), 2.99-3.24 (m, 2H), 2.44 (s, 3H), 2.13-2.36 (m, 1H), 1.57-1.73 (m, 2H). MS cald. for C25H24F3N2O3 [(M+H)+]: 457, obsd. 457.2.

Workup

  1. customThen, the solvent was removed
  2. filtrationThe resulting white precipitate was collected by filtration
  3. customdried under high vacuum

Sources & evidence

ORD record
ord-cab6a53d677649dbb043d6d94e331437
Source dataset
uspto-grants-2014_04
Patent number
US08691993B2

Reaction notes

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