Methanol → HCID 118080602, compound

HRID 1485772Notes

Reaction equation

HRID 1485772 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([C:12](=[O:14])[CH3:13])[C@@H:7]([CH3:15])[CH2:6][NH:5]2.Cl[C:17](Cl)([O:19][C:20](=[O:26])OC(Cl)(Cl)Cl)Cl.[F:28][C:29]1[CH:34]=[C:33]([F:35])C=[CH:31][C:30]=1O.CO>C(OCC)(=O)C>[C:12]([N:8]1[C:9]2[C:4](=[CH:3][C:2]([Br:1])=[CH:11][CH:10]=2)[N:5]([C:20]([O:19][C:17]2[CH:31]=[CH:30][C:29]([F:28])=[CH:34][C:33]=2[F:35])=[O:26])[CH2:6][C@@H:7]1[CH3:15])(=[O:14])[CH3:13]

Participants

6

Reactant 4

HCID 887MethanolHCID 94429TriphosgeneHCID 1230512,4-DifluorophenolHCID 118078861(S)-1-(6-bromo-2-methyl-3,4-dihydroquinoxalin-1(2H)-yl)ethanone

Product 1

HCID 118080602HCID 118080602, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A 1.5 mL reaction vial was charged with (S)-1-(6-bromo-2-methyl-3,4-dihydroquinoxalin-1(2H)-yl)ethan-1-one (0.2 M in 4:1:1,2-dichloroethane/N,N-disopropylethylamine, 100 μL, 0.02 mmol). Triphosgene (0.4 M solution in 1,2-dichloroethane, 20 μL, 0.008 mmol) was then added, and the reaction mixture was placed on a heater shaker at room temperature for 4 h. 2,4-Difluorophenol (0.2 M solution in 1,4-dioxane, 110 μl, 0.022 mmol) was then added, and the reaction was heated to 50° C. on a heater shaker overnight. Methanol (100 μl) was added and the reaction was placed on a heater shaker at 50° C. for 30 minutes. The reaction was diluted with ethyl acetate and washed with a saturated sodium bicarbonate solution. The aqueous layer was separated and washed with ethyl acetate and the combined organic layers were concentrated under a stream of nitrogen and vacuum. The crude product was purified by mass triggered preparatory HPLC. The product, 2,4-difluorophenyl (5)-4-acetyl-7-bromo-3-methyl-3,4-dihydroquinoxaline-1(2H)-carboxylate, was used without further purification.

Workup

  1. customA 1.5 mL reaction
  2. waitthe reaction was placed on a heater shaker at 50° C. for 30 minutes
  3. washwashed with a saturated sodium bicarbonate solution
  4. customThe aqueous layer was separated
  5. washwashed with ethyl acetate
  6. concentrationthe combined organic layers were concentrated under a stream of nitrogen and vacuum
  7. customThe crude product was purified by mass
  8. customThe product, 2,4-difluorophenyl (5)-4-acetyl-7-bromo-3-methyl-3,4-dihydroquinoxaline-1(2H)-carboxylate, was used without further purification

Sources & evidence

ORD record
ord-3f7a581d7f7d430aa0b300b972cbe543
Source dataset
uspto-grants-2016_08
Patent number
US09422281B2

Reaction notes

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