Methanol → (S)-2-(4-Fluorophenyl)-3-(2-methylpyrrolidin-1-yl)quinoxaline-6-carboxylic acid

HRID 717025Notes

Reaction equation

HRID 717025 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]([N:18]3[CH2:22][CH2:21][CH2:20][C@@H:19]3[CH3:23])=[N:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:24]([O:26]CCCC)=[O:25])[CH:14]=3)[N:9]=2)=[CH:4][CH:3]=1.CO.[OH-].[Na+]>O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]([N:18]3[CH2:22][CH2:21][CH2:20][C@@H:19]3[CH3:23])=[N:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:24]([OH:26])=[O:25])[CH:14]=3)[N:9]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 68063092(S)-butyl 2-(4-fluorophenyl)-3-(2-methylpyrrolidin-1-yl)quinoxaline-6-carboxylate

Product 1

HCID 50991311(S)-2-(4-Fluorophenyl)-3-(2-methylpyrrolidin-1-yl)quinoxaline-6-carboxylic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

Into a 10-mL sealed tube, was placed (S)-butyl 2-(4-fluorophenyl)-3-(2-methylpyrrolidin-1-yl)quinoxaline-6-carboxylate (150 mg, 0.37 mmol, 1.00 equiv), methanol (15 mL), sodium hydroxide (74 mg, 1.85 mmol, 5.02 equiv), water (2 mL). The resulting solution was stirred for 2 hrs at 50° C. in an oil bath. The resulting mixture was concentrated under vacuum and diluted with 20 mL of H2O. The pH value of the aqueous solution was adjusted to 4-5 with aq. hydrogen chloride (1 mol/L). The resulting solids were collected by filtration. The crude product (150 mg) was purified by Prep-HPLC with the following conditions (1#-Waters 2767-1): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, water with 0.05% TFA and CH3CN (60% CH3CN up to 75% in 8 min, up to 100% in 1.5 min); Detector, UV 220 254 nm. This resulted in 60 mg (46%) of (S)-2-(4-fluorophenyl)-3-(2-methylpyrrolidin-1-yl)quinoxaline-6-carboxylic acid as a yellow solid.

Workup

  1. customInto a 10-mL sealed tube
  2. concentrationThe resulting mixture was concentrated under vacuum
  3. additiondiluted with 20 mL of H2O
  4. filtrationThe resulting solids were collected by filtration
  5. customThe crude product (150 mg) was purified by Prep-HPLC with the following conditions (1#-Waters 2767-1)
  6. waitmobile phase, water with 0.05% TFA and CH3CN (60% CH3CN up to 75% in 8 min
  7. waitup to 100% in 1.5 min)
  8. customThis resulted in 60 mg (46%) of (S)-2-(4-fluorophenyl)-3-(2-methylpyrrolidin-1-yl)quinoxaline-6-carboxylic acid as a yellow solid

Sources & evidence

ORD record
ord-7cc6312810cd475a9ba4adca10d06acd
Source dataset
uspto-grants-2015_11
Patent number
US09193693B2

Reaction notes

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