Lithium hydroxide, monohydrate → HCID 71711190, compound

HRID 1468381Notes

Reaction equation

HRID 1468381 reaction equation
O.[OH-].[Li+].C[O:5][C:6](=[O:37])[CH2:7][C:8]1[C:17]([CH3:18])=[C:16]([C:19]2[CH:24]=[CH:23][C:22]([S:25]([C:28]3[CH:33]=[C:32]([F:34])[CH:31]=[C:30]([F:35])[CH:29]=3)(=[O:27])=[O:26])=[CH:21][CH:20]=2)[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([F:36])[CH:14]=2)[CH:9]=1>C1COCC1.O>[F:34][C:32]1[CH:33]=[C:28]([S:25]([C:22]2[CH:21]=[CH:20][C:19]([C:16]3[C:15]4[C:10](=[CH:11][CH:12]=[C:13]([F:36])[CH:14]=4)[CH:9]=[C:8]([CH2:7][C:6]([OH:37])=[O:5])[C:17]=3[CH3:18])=[CH:24][CH:23]=2)(=[O:27])=[O:26])[CH:29]=[C:30]([F:35])[CH:31]=1

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86694975HCID 86694975, compound

Product 1

HCID 71711190HCID 71711190, compoundYield 98.5%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

Lithium hydroxide monohydrate (0.019 g, 0.45 mmol) was added to a stirred solution of {4-[4-(3,5-difluorobenzenesulfonyl)-phenyl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid methyl ester (0.055 g, 0.11 mmol) in a 3:1 THF—H2O mixture (4 mL). The reaction mixture was stirred for 16 hours at room temperature. The THF was distilled off under reduced pressure, and the crude residue was diluted with water, acidified [pH˜2] via the drop-wise addition of an aqueous solution of hydrochloric acid (6.0 N). The mixture was extracted twice with ethyl acetate. The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product. Trituration with hexanes afforded {4-[4-(3,5-difluorobenzenesulfonyl)-phenyl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid (0.051 g, 96%) as a solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.48 (br. s., 1 H) 8.22 (d, J=7.82 Hz, 2 H) 7.97-8.05 (m, 1 H) 7.87-7.92 (m, 3 H) 7.74 (t, J=9.29 Hz, 1 H) 7.55 (d, J=7.82 Hz, 2 H) 7.35-7.42 (m, 1 H) 6.66 (d, J=11.74 Hz, 1 H) 3.84 (s, 2 H) 2.03 (s, 3 H) MS calcd. for C25H16F3O4S [(M−H)−] 469, obsd. 469.4.

Workup

  1. distillationThe THF was distilled off under reduced pressure
  2. additionthe crude residue was diluted with water
  3. additionvia the drop-wise addition of an aqueous solution of hydrochloric acid (6.0 N)
  4. extractionThe mixture was extracted twice with ethyl acetate
  5. washThe combined organic layers were washed with water and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customto give the crude product

Sources & evidence

ORD record
ord-bff59f1429894edab9a263d0c17a0eae
Source dataset
uspto-grants-2015_04
Patent number
US09000044B2

Reaction notes

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