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

HRID 2363837Notes

Reaction equation

HRID 2363837 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][CH:27]=[CH:26][C:25]=3[Cl:30])(=[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:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[S:21]([N:18]1[CH2:19][CH2:20][CH:15]([C:13]2[C:12]3[C:7](=[CH:8][CH:9]=[C:10]([F:31])[CH:11]=3)[CH:6]=[C:5]([CH2:4][C:3]([OH:32])=[O:2])[CH:14]=2)[CH2:16][CH2:17]1)(=[O:22])=[O:23]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86686897{4-[1-(2-Chloro-benzenesulfonyl)-piperidin-4-yl]-6-fluoro-naphthalen-2-yl}-acetic acid methyl ester

Product 1

HCID 71572193{4-[1-(2-Chloro-benzenesulfonyl)-piperidin-4-yl]-6-fluoro-naphthalen-2-yl}-acetic acidYield 46%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of {4-[1-(2-chloro-benzenesulfonyl)-piperidin-4-yl]-6-fluoro-naphthalen-2-yl}-acetic acid methyl ester (90 mg, 0.19 mmol) in THF (4 mL) was added a solution of lithium hydroxide monohydrate (40 mg, 0.95 mmol) in water (1 mL) and the reaction mixture was stirred for 24 h 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-(2-chloro-benzenesulfonyl)-piperidin-4-yl]-6-fluoro-naphthalen-2-yl}-acetic acid (40 mg, 46%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.36 (br. s., 1H), 8.03 (d, J=7.8 Hz, 1H), 7.88-7.99 (m, 2H), 7.67-7.79 (m, 3H), 7.61 (t, J=8.8 Hz, 1H), 7.40 (dt, J=8.7, 1.7 Hz, 1H), 7.35 (s, 1H), 3.88 (d, J=12.2 Hz, 2H), 3.72 (s, 2H), 3.46 (t, J=11.7 Hz, 1H), 3.04 (t, J=11.7 Hz, 2H), 1.88-1.96 (m, 2H), 1.64-1.79 (m, 2H); MS cald. for C23H22ClFNO4S [(M−H)−]: 462, obsd. 462.2.

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-dd9e5a95120647998b6c3ff8281aa245
Source dataset
uspto-grants-2014_04
Patent number
US08691993B2

Reaction notes

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