Lithium Hydroxide → 4-(2-(4,4-Dimethyl-1,2,3,4-tetrahydro-N-(4-methylphenyl)quinolin-7-yl)ethynyl)-2-fluorobenzoic Acid

HRID 1598969Notes

Reaction equation

HRID 1598969 reaction equation
[CH3:1][C:2]1([CH3:33])[C:11]2[C:6](=[CH:7][C:8]([C:12]#[C:13][C:14]3[CH:24]=[CH:23][C:17]([C:18]([O:20]CC)=[O:19])=[C:16]([F:25])[CH:15]=3)=[CH:9][CH:10]=2)[N:5]([C:26]2[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=2)[CH2:4][CH2:3]1.[Li+].[OH-]>O1CCCC1.CO>[CH3:1][C:2]1([CH3:33])[C:11]2[C:6](=[CH:7][C:8]([C:12]#[C:13][C:14]3[CH:24]=[CH:23][C:17]([C:18]([OH:20])=[O:19])=[C:16]([F:25])[CH:15]=3)=[CH:9][CH:10]=2)[N:5]([C:26]2[CH:27]=[CH:28][C:29]([CH3:32])=[CH:30][CH:31]=2)[CH2:4][CH2:3]1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 18931465Ethyl 4-(2-(4,4-Dimethyl-1,2,3,4-tetrahydro-N-(4-methylphenyl)quinolin-7-yl)ethynyl)-2-fluorobenzoate2×

Product 1

HCID 189314664-(2-(4,4-Dimethyl-1,2,3,4-tetrahydro-N-(4-methylphenyl)quinolin-7-yl)ethynyl)-2-fluorobenzoic AcidYield 98%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 0.088 g (0.19 mmol) of ethyl 4-(2-(4,4-dimethyl-1,2,3,4-tetrahydro-N-(4-methylphenyl) quinolin-7-yl)ethynyl)-2-fluorobenzoate (Compound 11) in 3.0 mL of tetrahydrofuran and 0.5 mL of methanol was added 0.5 mL (0.5 mmol) of 1.0M aqueous LiOH. The resulting solution was stirred at room temperature for 72 hours. The mixture was concentrated in vacuo, water was added, and the mixture was extracted with ethyl acetate (2x). The combined organic layers were washed with brine, dried (MgSO4), filtered, and concentrated in vacuo. The residue was purified by recrystallization from acetonitrile to give the title compound as a solid (77 mg, 90%). PNMR (300 MHz, d6-acetone) d 1.36 (6 H, s), 1.40 (3 H, t, J=7.1 Hz), 1.86 (2 H, t, J=5.9 Hz), 2.34 (3 H, s), 3.62 (2 H, t, J=5.9 Hz), 6.64 (1 H, d, J=1.6 Hz), 6.86 (1 H, dd, J=8.0, 1.6 Hz), ), 7.17 (2 H, d, J=8.3 Hz), 7.25-7.37 (5 H, m), 7.92 (1 H, t, J=7.8 Hz).

Workup

  1. concentrationThe mixture was concentrated in vacuo, water
  2. additionwas added
  3. extractionthe mixture was extracted with ethyl acetate (2x)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by recrystallization from acetonitrile

Sources & evidence

ORD record
ord-abc4d246483d4b699db5e908185189ff
Source dataset
uspto-grants-1998_04
Patent number
US05739338

Reaction notes

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