Lithium hydroxide, monohydrate → HCID 70817113, compound

HRID 1261766Notes

Reaction equation

HRID 1261766 reaction equation
C[O:2][C:3](=[O:29])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]2[C:20](=[O:21])[C:19]3[C:14](=[CH:15][C:16]([Cl:22])=[CH:17][CH:18]=3)[N:13]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=3)[CH:12]=2)=[CH:6][CH:5]=1.O.[OH-].[Li+]>O1CCCC1.O>[Cl:22][C:16]1[CH:15]=[C:14]2[C:19]([C:20](=[O:21])[C:11]([CH2:10][C:7]3[CH:6]=[CH:5][C:4]([C:3]([OH:29])=[O:2])=[CH:9][CH:8]=3)=[CH:12][N:13]2[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=2)=[CH:18][CH:17]=1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrate3×HCID 70816926HCID 70816926, compound

Product 1

HCID 70817113HCID 70817113, compoundYield 66.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 4-(7-chloro-4-oxo-1-pyridin-2-yl-1,4-dihydro-quinolin-3-ylmethyl)-benzoic acid methyl ester (28 mg, 69.2 μmol) in tetrahydrofuran (553 μL) at 25° C. was treated with a solution of lithium hydroxide monohydrate (5.8 mg, 138 μmol) in water (138 μL). The reaction was stirred at 25° C. for 24 h. At this time, LCMS indicated that the reaction was incomplete. The reaction was treated with additional lithium hydroxide monohydrate (5.8 mg, 138 μmol). The reaction was stirred overnight at 25° C. At this time, LCMS still indicated that the reaction was incomplete. The reaction was treated with a third portion of lithium hydroxide monohydrate (5.8 mg, 138 μmol). The reaction was stirred overnight at 25° C. At this time, the reaction was diluted with water (30 mL) and extracted with methylene chloride (1×30 mL). The aqueous layer was then acidified with a 1N aqueous hydrochloric acid solution and extracted with a 10% solution of methanol/methylene chloride (3×50 mL). These organics were dried over sodium sulfate, filtered and concentrated in vacuo to afford 4-(7-chloro-4-oxo-1-pyridin-2-yl-1,4-dihydro-quinolin-3-ylmethyl)-benzoic acid (18 mg, 66.6%) as a light brown solid. ES+-HRMS m/e calcd for C22H15ClN2O3 [M+H+] 391.0844. Found 391.0835; 1H NMR (400 MHz, DMSO-d6) δ ppm 12.79 (br. s., 1H) 8.73 (dd, J=4.8, 1.2 Hz, 1H) 8.29 (s, 1H) 8.17-8.25 (m, 1H) 7.77-7.86 (m, 3H) 7.68 (dd, J=7.1, 5.2 Hz, 1H) 7.41-7.48 (m, 3H) 7.22 (d, J=1.8 Hz, 1H) 3.88 (s, 1H).

Workup

  1. stirringThe reaction was stirred overnight at 25° C
  2. stirringThe reaction was stirred overnight at 25° C
  3. extractionextracted with methylene chloride (1×30 mL)
  4. extractionextracted with a 10% solution of methanol/methylene chloride (3×50 mL)
  5. dry with materialThese organics were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4f7cb584765a43f396738ec0be389c5a
Source dataset
uspto-grants-2013_06
Patent number
US08471027B2

Reaction notes

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