Hydrochloric Acid → (3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-phenyl)-acetic acid

HRID 1455230Notes

Reaction equation

HRID 1455230 reaction equation
C[O:2][C:3](=[O:38])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([C:11]2[CH:15]=[C:14]([C:16]3[N:17]([CH2:29][C:30]4[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:31]=4[F:37])[C:18](=[O:28])[C:19]([C:26]#[N:27])=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:21]=3)[S:13][CH:12]=2)[CH:6]=1.C1COCC1.O[Li].O.Cl>O>[C:26]([C:19]1[C:18](=[O:28])[N:17]([CH2:29][C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:31]=2[F:37])[C:16]([C:14]2[S:13][CH:12]=[C:11]([C:7]3[CH:6]=[C:5]([CH2:4][C:3]([OH:38])=[O:2])[CH:10]=[CH:9][CH:8]=3)[CH:15]=2)=[CH:21][C:20]=1[C:22]([F:24])([F:25])[F:23])#[N:27]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 67389181HCID 67389181, compound

Product 1

HCID 67388548(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-phenyl)-acetic acidYield 65.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
30 °C

Procedure

(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-phenyl)-acetic acid methyl ester (0.988 g, 1.81 mmoles) was dissolved into THF (20 mL) and water (6 mL). To this homogeneous mixture was then added LiOH hydrate (152 mg, 3.62 mmoles). This mix was then stirred at 30° C. for 2 hours. After this period the reaction mixture was acidified to pH˜3 using 1H HCl and was evaporated in vacuo. The resulting residue was extracted with DCM (3×15 mL) and the resulting organic layer was dried over anhydrous Na2SO4 and evaporated in vacuo to yield crude product. The crude product was purified using flash silica chromatography (0-5% MeOH/DCM) to yield (3-{5-[5-cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-phenyl)-acetic acid (625 mg, 65%) as a yellow solid. 1H-NMR (CDCl3): δ 7.64 (br d, J=1.5 Hz, 1H), 7.41-7.38 (m, 2H), 7.32-7.30 (m, 1H), 7.13-7.06 (m, 1H), 6.90-6.84 (m, 1H), 6.82-6.75 (m, 1H), 6.64 (s, 1H), 5.43 (s, 2H), 3.70 (s, 2H). MS(ES+): 531.1 (M+H).

Workup

  1. waitAfter this period the reaction mixture was acidified to pH˜3
  2. customwas evaporated in vacuo
  3. extractionThe resulting residue was extracted with DCM (3×15 mL)
  4. dry with materialthe resulting organic layer was dried over anhydrous Na2SO4
  5. customevaporated in vacuo
  6. customto yield crude product
  7. customThe crude product was purified

Sources & evidence

ORD record
ord-d1bd33802d8a4cc9a834d6e81f826596
Source dataset
uspto-grants-2009_01
Patent number
US07482366B2

Reaction notes

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