Lithium hydroxide, monohydrate → {4-[1-(3,5-Dichloro-benzenesulfonyl)-piperidin-4-yl]-6-fluoro-naphthalen-2-yl}-acetic acid

HRID 2363849Notes

Reaction equation

HRID 2363849 reaction equation
C[O:2][C:3](=[O:33])[CH2:4][C:5]1[CH:14]=[C:13]([CH:15]2[CH2:20][CH2:19][N:18]([S:21]([C:24]3[CH:29]=[C:28]([Cl:30])[CH:27]=[C:26]([Cl:31])[CH:25]=3)(=[O:23])=[O:22])[CH2:17][CH2:16]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>[Cl:31][C:26]1[CH:25]=[C:24]([S:21]([N:18]2[CH2:19][CH2:20][CH:15]([C:13]3[C:12]4[C:7](=[CH:8][CH:9]=[C:10]([F:32])[CH:11]=4)[CH:6]=[C:5]([CH2:4][C:3]([OH:33])=[O:2])[CH:14]=3)[CH2:16][CH2:17]2)(=[O:23])=[O:22])[CH:29]=[C:28]([Cl:30])[CH:27]=1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86686903HCID 86686903, compound

Product 1

HCID 71604110{4-[1-(3,5-Dichloro-benzenesulfonyl)-piperidin-4-yl]-6-fluoro-naphthalen-2-yl}-acetic acidYield 82%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of {4-[1-(3,5-dichloro-benzenesulfonyl)-piperidin-4-yl]-6-fluoro-naphthalen-2-yl}-acetic acid methyl ester (75 mg, 0.15 mmol) in THF (6 mL) was added a solution of lithium hydroxide monohydrate (30 mg, 0.7 mmol) in water (1.5 mL) and the reaction mixture was stirred for 24 hours at room temperature. The reaction mixture was concentrated under reduced pressure and washed with diethyl ether (3×5 mL). The washings were discarded. Water (5 mL) was added to the residue, and the mixture acidified (pH ˜2-3) with an aqueous solution of hydrochloric acid (2 N) and extracted with ethyl acetate (3×5 mL). The combined organic extracts were dried over Na2SO4 and evaporated under reduced pressure to give {4-[1-(3,5-dichloro-benzenesulfonyl)-piperidin-4-yl]-6-fluoro-naphthalen-2-yl}-acetic acid (60 mg, 82%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.35 (br s, 1H), 8.10 (s, 1H), 7.86-8.01 (m, 2H), 7.82 (s, 2H), 7.69 (s, 1H), 7.31-7.44 (m, 2H), 3.85 (d, J=12.2 Hz, 2H), 3.72 (s, 2H), 2.62-2.73 (m, 3H), 1.93 (d, J=12.2 Hz, 2H), 1.69-1.83 (m, 2H); MS cald. for C23H19Cl2FNO4S [(M−H)−]: 494, obsd. 494.2.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. washwashed with diethyl ether (3×5 mL)
  3. additionWater (5 mL) was added to the residue
  4. extractionextracted with ethyl acetate (3×5 mL)
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-83af6e9b7ba04f0b8d21ea8213aa739a
Source dataset
uspto-grants-2014_04
Patent number
US08691993B2

Reaction notes

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