Sodium Hydroxide → HCID 66799516, compound

HRID 404980Notes

Reaction equation

HRID 404980 reaction equation
[OH-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][O:17][C:18]3[CH:27]=[C:26]4[C:21]([CH2:22][CH2:23][N:24]([CH:29]5[CH2:33][CH2:32][CH2:31][CH2:30]5)[C:25]4=[O:28])=[CH:20][CH:19]=3)=[CH:12][CH:11]=2)=[CH:6][C:5]=1[C:34]([O:36]C)=[O:35]>O1CCOCC1>[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][O:17][C:18]3[CH:27]=[C:26]4[C:21]([CH2:22][CH2:23][N:24]([CH:29]5[CH2:33][CH2:32][CH2:31][CH2:30]5)[C:25]4=[O:28])=[CH:20][CH:19]=3)=[CH:12][CH:11]=2)=[CH:6][C:5]=1[C:34]([OH:36])=[O:35]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 66799480HCID 66799480, compound

Product 1

HCID 66799516HCID 66799516, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

50% Aqueous NaOH (0.5 mL, 0.6 mmol) was added to a solution of the crude ester (0.150 g, 0.3 mmol) in dioxane (5 mL). The reaction mixture was heated to reflux for 1 h, and then cooled to room temperature. Excess solvent was removed under reduced pressure. The residue was diluted with water and then acidified using 1M HCl. Extraction using ethyl acetate, followed by silica gel column chromatography afforded 4-chloro-4′-((2-cyclopentyl-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yloxy)methyl)biphenyl-3-carboxylic acid as colorless solid (0.125 g, 88%). Final HPLC purification was performed using isopropyl alcohol (IPA):H2O solvent system. 1H NMR (400 MHz, DMSO-d6): δ 8.00 (s, 1H), 7.60-7.78 (m, 2H), 7.63-7.45 (m, 5H), 7.15 (d, 1H, J=8.6 Hz)), 7.09 (d, 1H, J=8.6 Hz), 5.17 (s, 2H), 4.97-4.93 (m, 1H), 3.34 (t, 2H, J=6.1 Hz), 2.86 (t, 2H, J=6.1 Hz), 1.65-1.50 (m, 8H). LC-MS (ESI) Calcd for C28H26ClNO4 [M+H]+: 476.16. Found: 475.95. HRMS (ESI) calcd for C28H26ClNO4 [M+H]+: 476.1623. Found: 476.1621.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 1 h
  3. customExcess solvent was removed under reduced pressure
  4. additionThe residue was diluted with water
  5. extractionExtraction

Sources & evidence

ORD record
ord-47a1b9ae06ba46bc9ec3faf7eef47819
Source dataset
uspto-grants-2014_06
Patent number
US08748632B2

Reaction notes

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