Lithium hydroxide, monohydrate → HCID 71603268, compound

HRID 2363888Notes

Reaction equation

HRID 2363888 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[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=3[Cl: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>[Cl:31][C:25]1[CH:26]=[C:27]([Cl:30])[CH:28]=[CH:29][C:24]=1[NH:23][C:22]([N:19]1[CH2:18][CH2:17][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])[CH2:21][CH2:20]1)=[O:32]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86686924HCID 86686924, compound

Product 1

HCID 71603268HCID 71603268, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of {4-[1-(2,4-dichloro-phenylcarbamoyl)-piperidin-4-yl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid methyl ester (74.8 mg, 0.149 mmol) in THF (8.0 mL) was added a solution of lithium hydroxide monohydrate (71.4 mg, 1.7 mmol) in water (2.0 mL) at room temperature. The resulting solution was stirred overnight at room temperature under a nitrogen atmosphere. The solvent was evaporated. Water (˜20 mL) was added and the mixture was neutralized with 1.0 N HCl (30 mL). The resulting white precipitate was collected by filtration and dried under high vacuum overnight to provide {4-[1-(2,4-dichloro-phenylcarbamoyl)-piperidin-4-yl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid (57.8 mg, 80%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.5 (br. s, 1H), 8.46 (br. s, 1H), 7.90 (dd, J=8.80, 6.50 Hz, 1H), 7.76-7.86 (m, 1H), 7.68 (m, 2H), 7.50 (d, J=8.78 Hz, 1H), 7.40 (dd, J=8.70, 2.30 Hz, 1H), 7.30-7.37 (m, 1H), 4.20-4.32 (m, 2H), 3.68-3.97 (m, 4H), 3.02-3.24 (m, 2H), 2.43 (s, 3H), 2.16-2.40 (m, 2H), 1.61-1.70 (m, 2H). MS cald. for C25H24Cl2FN2O3 [(M+H)+]: 489, obsd. 489.1.

Workup

  1. customThe solvent was evaporated
  2. additionWater (˜20 mL) was added
  3. filtrationThe resulting white precipitate was collected by filtration
  4. customdried under high vacuum overnight

Sources & evidence

ORD record
ord-53b09a19e72b4af8b6fcb0c2f699e519
Source dataset
uspto-grants-2014_04
Patent number
US08691993B2

Reaction notes

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