Sodium Hydroxide → 2-(4-Fluorophenyl)-3-(3-(methoxymethyl)piperidin-1-yl)quinoxaline-6-carboxylic acid

HRID 717032Notes

Reaction equation

HRID 717032 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]([N:18]3[CH2:23][CH2:22][CH2:21][CH:20]([CH2:24][O:25][CH3:26])[CH2:19]3)=[N:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:27]([O:29]C)=[O:28])[CH:14]=3)[N:9]=2)=[CH:4][CH:3]=1.[OH-].[Na+]>CO.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]([N:18]3[CH2:23][CH2:22][CH2:21][CH:20]([CH2:24][O:25][CH3:26])[CH2:19]3)=[N:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:27]([OH:29])=[O:28])[CH:14]=3)[N:9]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 67042016Methyl 2-(4-fluorophenyl)-3-(3-(methoxymethyl)piperidin-1-yl)quinoxaline-6-carboxylate

Product 1

HCID 509913992-(4-Fluorophenyl)-3-(3-(methoxymethyl)piperidin-1-yl)quinoxaline-6-carboxylic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Into a 50-mL round-bottom flask, was placed a solution of methyl 2-(4-fluorophenyl)-3-(3-(methoxymethyl)piperidin-1-yl)quinoxaline-6-carboxylate (152.3 mg, 0.37 mmol, 1.00 equiv) in methanol (15 mL). This was followed by the addition of a solution of sodium hydroxide (44.7 mg, 1.12 mmol, 3.00 equiv) in water (1.5 mL) dropwise with stirring. The resulting solution was stirred for 4 h at 50° C. in an oil bath. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with water. The pH value of the aqueous solution was adjusted to 3-4 with 1N hydrogen chloride. The resulting solids were collected by filtration and the crude product (240 mg) was purified by Prep-HPLC under the following conditions (AGILENT Pre-HPLC (UV-Directed)): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, water with 0.05% TFA and CH3CN (45% CH3CN up to 60% in 8 min, hold 60% in 5 min, up to 100% in 0.1 min, hold 100% in 1.4 min); Detector, uv 220&254 nm. This resulted in 89 mg (61%) of 2-(4-fluorophenyl)-3-(3-(methoxymethyl)piperidin-1-yl)quinoxaline-6-carboxylic acid as a yellow solid.

Workup

  1. customInto a 50-mL round-bottom flask, was placed
  2. stirringThe resulting solution was stirred for 4 h at 50° C. in an oil bath
  3. concentrationThe resulting mixture was concentrated under vacuum
  4. additionThe resulting solution was diluted with water
  5. filtrationThe resulting solids were collected by filtration
  6. customthe crude product (240 mg) was purified by Prep-HPLC under the following conditions (AGILENT Pre-HPLC (UV-Directed))
  7. customin 5 min
  8. waitup to 100% in 0.1 min
  9. customin 1.4 min
  10. customThis resulted in 89 mg (61%) of 2-(4-fluorophenyl)-3-(3-(methoxymethyl)piperidin-1-yl)quinoxaline-6-carboxylic acid as a yellow solid

Sources & evidence

ORD record
ord-47c8084de33640dbb224b9cfbbfa41b6
Source dataset
uspto-grants-2015_11
Patent number
US09193693B2

Reaction notes

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