Lithium hydroxide, monohydrate → 2-(3-Trifluoromethyl-5-fluoro-phenylamino)-non-8-enoic acid

HRID 553449Notes

Reaction equation

HRID 553449 reaction equation
C[O:2][C:3](=[O:24])[CH:4]([NH:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[C:15]([C:20]([F:23])([F:22])[F:21])[CH:14]=1)[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH:10]=[CH2:11].O.[OH-].[Li+]>O1CCCC1.O>[F:22][C:20]([F:21])([F:23])[C:15]1[CH:14]=[C:13]([NH:12][CH:4]([CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH:10]=[CH2:11])[C:3]([OH:24])=[O:2])[CH:18]=[C:17]([F:19])[CH:16]=1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 669153962-(3-Trifluoromethyl-5-fluoro-phenylamino)-non-8-enoic acid methyl ester

Product 1

HCID 669154392-(3-Trifluoromethyl-5-fluoro-phenylamino)-non-8-enoic acidYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-(3-Trifluoromethyl-5-fluoro-phenylamino)-non-8-enoic acid methyl ester (1.643 g, 4.73 mmol., 1 eq.) was dissolved in tetrahydrofuran (40 mL). A solution of lithium hydroxide monohydrate (0.596 g, 14.19 mmol., 3 eq.) in water (40 mL) was added dropwise and the reaction mixture stirred for a further 3 hours at ambient temperature by when LCMS analysis of an aliquot showed the reaction to be complete. The reaction mixture volume was reduced by half in vacuo to remove most of the tetrahydrofuran and the obtained solution was diluted with 1.5M hydrochloric acid (40 mL). The solution was extracted with dichloromethane (2×60 mL). The organic extracted were combined, dried over sodium sulfate and the solvent removed in vacuo to give 1.41 g (90%) of the title compound as a yellow oil. 1H NMR (500 MHz, CDCl3) δ ppm 6.68 (d, J=8.54 Hz, 1 H), 6.63 (s, 1 H), 6.44 (dd, J=1.98, 10.68 Hz, 1 H), 5.72-5.85 (m, J=6.64, 6.64, 10.28, 17.03 Hz, 1 H), 5.00 (dq, J=1.66, 17.15 Hz, 1 H), 4.95 (dt, J=0.97, 10.11 Hz, 1 H), 4.07 (dd, J=5.80, 6.87 Hz, 1 H), 2.19 (s, 2 H), 2.05 (q, J=6.87 Hz, 2 H), 1.90-1.99 (m, 1 H), 1.74-1.86 (m, 1 H), 1.43-1.51 (m, 2 H), 1.32-1.43 (m, 3 H). LC-MS: purity 98% (UV), tR 2.33 min, m/z [M+H]+334.10

Workup

  1. customthe reaction
  2. customto remove most of the tetrahydrofuran
  3. additionthe obtained solution was diluted with 1.5M hydrochloric acid (40 mL)
  4. extractionThe solution was extracted with dichloromethane (2×60 mL)
  5. extractionThe organic extracted
  6. dry with materialdried over sodium sulfate
  7. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-a9dc6986921748808f38ec22b6a5c7fd
Source dataset
uspto-grants-2011_11
Patent number
US08048862B2

Reaction notes

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