Lithium hydroxide, monohydrate → HCID 71603265, compound

HRID 2363884Notes

Reaction equation

HRID 2363884 reaction equation
C[O:2][C:3](=[O:33])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([CH:16]2[CH2:21][CH2:20][N:19]([C:22](=[O:31])[C:23]3[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:24]=3[F:30])[CH2:18][CH2:17]2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:32])[CH:11]=2)[CH:6]=1.O.[OH-].[Li+]>C1COCC1.O>[F:30][C:24]1[CH:25]=[CH:26][C:27]([F:29])=[CH:28][C:23]=1[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:32])[CH:11]=3)[CH:6]=[C:5]([CH2:4][C:3]([OH:33])=[O:2])[C:14]=2[CH3:15])[CH2:17][CH2:18]1)=[O:31]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86686922HCID 86686922, compound

Product 1

HCID 71603265HCID 71603265, compoundYield 81.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of {4-[1-(2,5-difluoro-benzoyl)-piperidin-4-yl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid methyl ester (73 mg, 0.160 mmol) in THF (8.0 mL) was added a solution of lithium hydroxide monohydrate (76.6 mg, 1.8 mmol) in water (2 mL). The reaction mixture was stirred at room temperature overnight. After this time, the reaction mixture was concentrated. Water (˜20 mL) was added and the mixture was acidified with 1.0 N aqueous HCl (3.2 mL). The resulting white precipitate was collected by vacuum filtration, washed with hexanes, and then further dried under vacuum to give {4-[1-(2,5-difluoro-benzoyl)-piperidin-4-yl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid (57.5 mg, 81%). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.46 (br. s, 1H), 7.80-8.20 (m, 1H), 7.90 (dd, J=9.00, 6.50 Hz, 1H), 7.69 (s, 1H), 7.31-7.52 (m, 4H), 4.62-4.77 (m, 1H), 3.68-4.08 (m, 4H), 3.48-3.60 (m, 1H), 2.95-3.21 (m, 1H), 2.43 (br. s., 3H), 2.11-2.34 (m, 2H), 1.57-1.82 (m, 2H). MS cald. for C25H23F3NO3 [(M+H)+]: 442, obsd. 442.2.

Workup

  1. concentrationAfter this time, the reaction mixture was concentrated
  2. additionWater (˜20 mL) was added
  3. filtrationThe resulting white precipitate was collected by vacuum filtration
  4. washwashed with hexanes
  5. customfurther dried under vacuum

Sources & evidence

ORD record
ord-7cf2bd4e696f4ee1bab081e322b34d70
Source dataset
uspto-grants-2014_04
Patent number
US08691993B2

Reaction notes

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