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

HRID 2363841Notes

Reaction equation

HRID 2363841 reaction equation
C[O:2][C:3](=[O:32])[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]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=3)(=[O:23])=[O:22])[CH2:17][CH2:16]2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:31])[CH:11]=2)[CH:6]=1.O.[OH-].[Li+]>C1COCC1.O>[Cl:30][C:27]1[CH:26]=[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:31])[CH:11]=4)[CH:6]=[C:5]([CH2:4][C:3]([OH:32])=[O:2])[CH:14]=3)[CH2:16][CH2:17]2)(=[O:22])=[O:23])=[CH:29][CH:28]=1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86686899HCID 86686899, compound

Product 1

HCID 71604044{4-[1-(4-Chloro-benzenesulfonyl)-piperidin-4-yl]-6-fluoro-naphthalen-2-yl}-acetic acidYield 72.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of {4-[1-(4-chloro-benzenesulfonyl)-piperidin-4-yl]-6-fluoro-naphthalen-2-yl}-acetic acid methyl ester (80 mg, 0.17 mmol) in THF (4 mL) was added a solution of lithium hydroxide monohydrate (35 mg, 0.83 mmol) in water (1 mL) and the reaction mixture was stirred for 24 h at RT. 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-(4-chloro-benzenesulfonyl)-piperidin-4-yl]-6-fluoro-naphthalen-2-yl}-acetic acid (57 mg, 65%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.27 (br s, 1H), 7.95 (dd, J=9.0, 6.1 Hz, 1H), 7.88 (d, J=10.3 Hz, 1H), 7.76-7.85 (m, 4H), 7.68 (s, 1H), 7.34-7.41 (m, 2H), 3.80 (d, J=11.2 Hz, 2H), 3.71 (s, 2H), 2.59 (t, J=11.2 Hz, 2H), 1.87-1.94 (m, 3H), 1.73-1.82 (m, 2H); MS cald. for C23H20ClFNO4S [(M−H)−]: 460, obsd. 460.3.

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-9754333fd1274f6e9eddc0bceff725a3
Source dataset
uspto-grants-2014_04
Patent number
US08691993B2

Reaction notes

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