Lithium hydroxide, monohydrate → HCID 71603339, compound

HRID 2363894Notes

Reaction equation

HRID 2363894 reaction equation
C[O:2][C:3](=[O:36])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([CH:16]2[CH2:21][CH2:20][N:19]([C:22](=[O:34])[NH:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=3)[CH2:18][CH2:17]2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:35])[CH:11]=2)[CH:6]=1.O.[OH-].[Li+]>C1COCC1.O>[F:35][C:10]1[CH:11]=[C:12]2[C:7](=[CH:8][CH:9]=1)[CH:6]=[C:5]([CH2:4][C:3]([OH:36])=[O:2])[C:14]([CH3:15])=[C:13]2[CH:16]1[CH2:21][CH2:20][N:19]([C:22](=[O:34])[NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:31])([F:33])[F:32])[CH:25]=2)[CH2:18][CH2:17]1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86686927HCID 86686927, compound

Product 1

HCID 71603339HCID 71603339, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of {6-fluoro-3-methyl-4-[1-(3-trifluoromethyl-phenylcarbamoyl)-piperidin-4-yl]-naphthalen-2-yl}-acetic acid methyl ester (97 mg, 0.193 mmol) in THF (8.0 mL) was added a solution of lithium hydroxide monohydrate (92.4 mg, 2.2 mmol) in water (2.0 mL) at room temperature. The resulting solution was stirred for four hours under a nitrogen atmosphere. The solvent was evaporated. Water (˜25 mL) was added and the mixture was acidified with 1.0 N aqueous HCl (3.9 mL). The resulting white precipitate was collected by filtration, washed with water and hexanes, and dried under high vacuum to provide {6-fluoro-3-methyl-4-[1-(3-trifluoromethyl-phenylcarbamoyl)-piperidin-4-yl]-naphthalen-2-yl}-acetic acid (65.8 mg, 70%). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.50 (br. s, 1H), 8.97 (br. s, 1H), 8.00-8.22 (m, 1H), 7.97 (s, 1H), 7.90 (dd, J=9.10, 6.50 Hz, 1H), 7.78 (d, J=8.50 Hz, 1H), 7.66-7.73 (m, 1H), 7.49 (t, J=8.30 Hz, 1H), 7.30-7.38 (m, 1H), 7.28 (d, J=8.30 Hz, 1H), 4.28-4.36 (m, 2H), 3.71-3.85 (m, 3H), 3.01-3.18 (m, 2H), 2.43 (s, 3H), 2.17-2.34 (m, 1H), 1.64-1.73 (m, 2H). MS cald. for C26H25F4N2O3 [(M+H)+]: 489, obsd. 489.2.

Workup

  1. customThe solvent was evaporated
  2. additionWater (˜25 mL) was added
  3. filtrationThe resulting white precipitate was collected by filtration
  4. washwashed with water and hexanes
  5. customdried under high vacuum

Sources & evidence

ORD record
ord-352f8b6cce054fe28ebfc0f796502298
Source dataset
uspto-grants-2014_04
Patent number
US08691993B2

Reaction notes

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