Methanol → (R)-2-Phenyl-3-(2-(trifluoromethyl)pyrrolidin-1-yl)quinoxaline-6-carboxylic acid

HRID 1405563Notes

Reaction equation

HRID 1405563 reaction equation
[C:1]1([C:7]2[C:16]([N:17]3[CH2:21][CH2:20][CH2:19][C@@H:18]3[C:22]([F:25])([F:24])[F:23])=[N:15][C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:26]([O:28]C)=[O:27])[CH:13]=3)[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+].CO>O>[C:1]1([C:7]2[C:16]([N:17]3[CH2:21][CH2:20][CH2:19][C@@H:18]3[C:22]([F:25])([F:23])[F:24])=[N:15][C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:26]([OH:28])=[O:27])[CH:13]=3)[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 67980708(R)-methyl 2-phenyl-3-(2-(trifluoromethyl)pyrrolidin-1-yl)quinoxaline-6-carboxylate

Product 1

HCID 50991305(R)-2-Phenyl-3-(2-(trifluoromethyl)pyrrolidin-1-yl)quinoxaline-6-carboxylic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

Into a 25-mL round-bottom flask, was placed (R)-methyl 2-phenyl-3-(2-(trifluoromethyl)pyrrolidin-1-yl)quinoxaline-6-carboxylate (40 mg, 0.10 mmol, 1.00 equiv), sodium hydroxide (20 mg, 0.50 mmol, 5.00 equiv), methanol (5 mL), water (1 mL). The resulting solution was stirred for 5 hs at 50° C. in an oil bath. The resulting mixture was concentrated under vacuum. The residue was diluted in 5 mL of water. The PH value was aqueous solution was adjusted to 4 with aq hydrochloric acid (1N). The resulting solids were collected by filtration. The crude product (50 mg) was purified by Prep-HPLC with the following conditions (1#-Waters 2767-1): Column, SunFire Prep C18, 5 um, 19*150 mm; mobile phase, water with 0.05% TFA and CH3CN (60% CH3CN up to 90% in 8 min, up to 100% in 1.5 min); Detector, UV 220 254 nm. This resulted in 12 mg (30%) of (R)-2-phenyl-3-(2-(trifluoromethyl)pyrrolidin-1-yl)quinoxaline-6-carboxylic acid as a yellow solid.

Workup

  1. customInto a 25-mL round-bottom flask, was placed
  2. concentrationThe resulting mixture was concentrated under vacuum
  3. additionThe residue was diluted in 5 mL of water
  4. filtrationThe resulting solids were collected by filtration
  5. customThe crude product (50 mg) was purified by Prep-HPLC with the following conditions (1#-Waters 2767-1)
  6. waitup to 100% in 1.5 min)
  7. customThis resulted in 12 mg (30%) of (R)-2-phenyl-3-(2-(trifluoromethyl)pyrrolidin-1-yl)quinoxaline-6-carboxylic acid as a yellow solid

Sources & evidence

ORD record
ord-06f1d22c934e4e17a1832772d266fd1e
Source dataset
uspto-grants-2014_12
Patent number
US08916560B2

Reaction notes

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