Lithium hydroxide, monohydrate → HCID 71604113, compound

HRID 2363855Notes

Reaction equation

HRID 2363855 reaction equation
C[O:2][C:3](=[O:27])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([CH:16]2[CH2:21][CH2:20][N:19]([S:22]([CH3:25])(=[O:24])=[O:23])[CH2:18][CH2:17]2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:26])[CH:11]=2)[CH:6]=1.O.[OH-].[Li+]>C1COCC1.O>[F:26][C:10]1[CH:11]=[C:12]2[C:7](=[CH:8][CH:9]=1)[CH:6]=[C:5]([CH2:4][C:3]([OH:27])=[O:2])[C:14]([CH3:15])=[C:13]2[CH:16]1[CH2:21][CH2:20][N:19]([S:22]([CH3:25])(=[O:23])=[O:24])[CH2:18][CH2:17]1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86686906HCID 86686906, compound

Product 1

HCID 71604113HCID 71604113, compoundYield 97.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of [6-fluoro-4-(1-methanesulfonyl-piperidin-4-yl)-3-methyl-naphthalen-2-yl]-acetic acid methyl ester (51 mg, 0.13 mmol) in THF (6.0 mL) was added a solution of lithium hydroxide monohydrate (62.1 mg, 2.6 mmol) in water (1.5 mL). The resulting solution was stirred for 15 hours at room temperature. The solvent was removed under vacuum. The residue was diluted with water (˜20 mL) and neutralized with 1.0 N aqueous HCl to form a suspension. The product was extracted into ethyl acetate (2×50 mL). The combined extracts were washed with brine, dried over anhydrous MgSO4, filtered, and concentrated to give a crude solid which was triturated with dichloromethane and hexanes. The solids were collected by filtration and washed with hexanes. After air drying, [6-fluoro-4-(1-methanesulfonyl-piperidin-4-yl)-3-methyl-naphthalen-2-yl]-acetic acid (48 mg, 94%) was obtained as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.4 (br. s, 1H), 7.91 (dd, J=8.91, 6.65 Hz, 2H), 7.70 (s, 1H), 7.36 (t, J=8.41 Hz, 1H), 3.78 (br. s, 6H), 2.95 (s, 3H), 2.26-2.47 (m, 6H), 1.75 (d, J=12.05 Hz, 2H). MS cald. for C19H23FNO4S [(M+H)+] 380, obsd. 380.0.

Workup

  1. customThe solvent was removed under vacuum
  2. additionThe residue was diluted with water (˜20 mL)
  3. customto form a suspension
  4. extractionThe product was extracted into ethyl acetate (2×50 mL)
  5. washThe combined extracts were washed with brine
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a crude solid which
  10. customwas triturated with dichloromethane and hexanes
  11. filtrationThe solids were collected by filtration
  12. washwashed with hexanes
  13. customAfter air drying

Sources & evidence

ORD record
ord-9bf073ff0ccc40ccbae84a9f658067f6
Source dataset
uspto-grants-2014_04
Patent number
US08691993B2

Reaction notes

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