Lithium hydroxide, monohydrate → HCID 71711193, compound

HRID 1468375Notes

Reaction equation

HRID 1468375 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[C:33]([F:34])=[CH:32][CH:31]=[CH:30][C:29]=3[F:35])(=[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:35][C:29]1[CH:30]=[CH:31][CH:32]=[C:33]([F:34])[C:28]=1[S:25]([C:22]1[CH:21]=[CH:20][C:19]([C:16]2[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([F:36])[CH:14]=3)[CH:9]=[C:8]([CH2:7][C:6]([OH:37])=[O:5])[C:17]=2[CH3:18])=[CH:24][CH:23]=1)(=[O:26])=[O:27]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86694969HCID 86694969, compound

Product 1

HCID 71711193HCID 71711193, compoundYield 80%

Reagents, catalysts & solvents 1

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

Procedure

Lithium hydroxide monohydrate (0.011 g, 0.26 mmol) was added to a stirred solution of {4-[4-(2,6-difluorobenzenesulfonyl)-phenyl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid methyl ester (0.031 g, 0.064 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-(2,6-difluorobenzenesulfonyl)-phenyl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid (0.024 g, 80%) as a solid. The final product was isolated with a significant amount of water as an impurity. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.17 (d, J=7.91 Hz, 2 H), 8.01 (dd, J=9.23, 6.22 Hz, 1 H), 7.91 (s, 1 H), 7.80-7.88 (m, 1 H), 7.58 (d, J=8.48 Hz, 2 H), 7.39 (t, J=9.04 Hz, 3 H), 6.64 (d, J=11.87 Hz, 1 H), 3.83 (s, 2 H), 2.04 (s, 3 H). MS calcd. for C25H16F3O4S [(M−H)−] 469, obsd. 469.2.

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-d7efa9c2293044c19c101c0730558e26
Source dataset
uspto-grants-2015_04
Patent number
US09000044B2

Reaction notes

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