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

HRID 2363825Notes

Reaction equation

HRID 2363825 reaction equation
C[O:2][C:3](=[O:31])[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][CH:27]=[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:30])[CH:11]=2)[CH:6]=1.O.[OH-].[Li+]>C1COCC1.O>[C:24]1([S:21]([N:18]2[CH2:17][CH2:16][CH:15]([C:13]3[C:12]4[C:7](=[CH:8][CH:9]=[C:10]([F:30])[CH:11]=4)[CH:6]=[C:5]([CH2:4][C:3]([OH:31])=[O:2])[CH:14]=3)[CH2:20][CH2:19]2)(=[O:23])=[O:22])[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86686892[4-(1-Benzenesulfonyl-piperidin-4-yl)-6-fluoro-naphthalen-2-yl]-acetic acid methyl ester

Product 1

HCID 71603975[4-(1-Benzenesulfonyl-piperidin-4-yl)-6-fluoro-naphthalen-2-yl]-acetic acidYield 40.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of [4-(1-benzenesulfonyl-piperidin-4-yl)-6-fluoro-naphthalen-2-yl]-acetic acid methyl ester (90 mg, 0.2 mmol) in THF (8 mL) was added a solution of lithium hydroxide monohydrate (26 mg, 0.6 mmol) in water (2 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-benzenesulfonyl-piperidin-4-yl)-6-fluoro-naphthalen-2-yl]-acetic acid (35 mg, 40%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.36 (br s, 1H), 7.92-7.98 (m, 1H), 7.88 (d, J=11.2 Hz, 1H), 7.81 (d, J=7.8 Hz, 2H), 7.76 (d, J=6.8 Hz, 1H), 7.65-7.73 (m, 3H), 7.33-7.42 (m, 2H), 3.82 (d, J=11.7 Hz, 2H), 3.71 (s, 2H), 1.90 (d, J=11.2 Hz, 2H), 1.69-1.82 (m, 2H); MS cald. for C23H23FNO4S [(M−H)−]: 426, obsd. 426.2.

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-83043c2772aa4e28bd143c217e3fc72b
Source dataset
uspto-grants-2014_04
Patent number
US08691993B2

Reaction notes

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