Lithium hydroxide, monohydrate → {6-Fluoro-3-methyl-4-[4-(toluene-2-sulfonyl)-phenyl]-naphthalen-2-yl}-acetic acid

HRID 1468355Notes

Reaction equation

HRID 1468355 reaction equation
C[O:2][C:3](=[O:33])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([C:16]2[CH:21]=[CH:20][C:19]([S:22]([C:25]3[C:26]([CH3:31])=[CH:27][CH:28]=[CH:29][CH:30]=3)(=[O:24])=[O:23])=[CH:18][CH:17]=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>[F:32][C:10]1[CH:11]=[C:12]2[C:7](=[CH:8][CH:9]=1)[CH:6]=[C:5]([CH2:4][C:3]([OH:33])=[O:2])[C:14]([CH3:15])=[C:13]2[C:16]1[CH:21]=[CH:20][C:19]([S:22]([C:25]2[C:26]([CH3:31])=[CH:27][CH:28]=[CH:29][CH:30]=2)(=[O:23])=[O:24])=[CH:18][CH:17]=1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86694947{6-Fluoro-3-methyl-4-[4-(toluene-2-sulfonyl)-phenyl]-naphthalen-2-yl}-acetic acid methyl ester

Product 1

HCID 71712075{6-Fluoro-3-methyl-4-[4-(toluene-2-sulfonyl)-phenyl]-naphthalen-2-yl}-acetic acidYield 55.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of {6-fluoro-3-methyl-4-[4-(toluene-2-sulfonyl)-phenyl]-naphthalen-2-yl}-acetic acid methyl ester (20 mg, 0.04 mmol) in THF (5 mL) was added a solution of lithium hydroxide monohydrate (19.3 mg, 0.46 mmol) in water (1 mL) at room temperature. The resulting clear solution was stirred for 15 hours and then THF was removed under vacuum. Water (30 mL) was added and the mixture was acidified with 1.0N hydrochloric acid. The resulting solids were collected by filtration and washed with water and hexanes. After drying in air, {6-fluoro-3-methyl-4-[4-(toluene-2-sulfonyl)-phenyl]-naphthalen-2-yl}-acetic acid (10 mg, 52%) was isolated as off-white solid. 1H NMR (400 MHz, Methanol-d4) δ ppm 8.27 (d, J=7.9 Hz, 1 H), 8.04 (d, J=8.2 Hz, 2 H), 7.88 (dd, J=8.8, 6.0 Hz, 1 H), 7.81 (s, 1 H), 7.61 (t, J=7.5 Hz, 1 H), 7.48-7.55 (m, 1 H), 7.48 (d, J=8.2 Hz, 2 H), 7.40 (d, J=7.5 Hz, 1 H), 7.22 (td, J=8.8, 2.1 Hz, 1H), 6.65 (dd, J=11.2, 2.1 Hz, 1 H), 3.86 (s, 2 H), 2.52 (s, 3 H), 2.11 (s, 3 H). HRMS (ES−) calcd. for C26H20FO4S [(M−H)−] 447.1072, obsd. 447.1070.

Workup

  1. customTHF was removed under vacuum
  2. additionWater (30 mL) was added
  3. filtrationThe resulting solids were collected by filtration
  4. washwashed with water and hexanes
  5. customAfter drying in air

Sources & evidence

ORD record
ord-b881b36d90de4cafb508aee448b2ab22
Source dataset
uspto-grants-2015_04
Patent number
US09000044B2

Reaction notes

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