Potassium Carbonate → 4-(4-cyclopropylethynyl-2-oxo-4-trifluoromethyl-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yloxy)-butyric Acid Ethyl Ester

HRID 29015Notes

Reaction equation

HRID 29015 reaction equation
[CH:1]1([C:4]#[C:5][C:6]2([C:18]([F:21])([F:20])[F:19])[O:11][C:10](=[O:12])[NH:9][C:8]3[CH:13]=[CH:14][C:15]([OH:17])=[CH:16][C:7]2=3)[CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:29][CH2:30][CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33]>C1OCCOCCOCCOCCOCCOC1.CC(C)=O>[CH2:35]([O:34][C:32](=[O:33])[CH2:31][CH2:30][CH2:29][O:17][C:15]1[CH:14]=[CH:13][C:8]2[NH:9][C:10](=[O:12])[O:11][C:6]([C:5]#[C:4][CH:1]3[CH2:3][CH2:2]3)([C:18]([F:20])([F:21])[F:19])[C:7]=2[CH:16]=1)[CH3:36]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 76300Ethyl 4-bromobutyrateHCID 114264734-Cyclopropylethynyl-6-hydroxy-4-trifluoromethyl-1,4-dihydro-benzo [d][1,3]oxazin-2-one

Product 1

HCID 688064764-(4-cyclopropylethynyl-2-oxo-4-trifluoromethyl-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yloxy)-butyric Acid Ethyl EsterYield 39.3%

Reagents, catalysts & solvents 2

HCID 2855718-Crown-6CatalystHCID 180AcetoneSolvent

Conditions

Temperature
56 °C

Procedure

To 120 mg (0.40 mmol) of 9 were added 12 mL of anhydrous acetone, 120 mg (0.86 mmol) of anhydrous potassium carbonate, 2 mg of 18-crown-6 and 40 μL (0.28 mmol) of ethyl 4-bromobutyrate. The reaction mixture was allowed to stir at 56° C. for 3 hours and was concentrated under reduced pressure. To the residue 20 mL of water were added followed by 1 mL of 1N HCl. The aqueous layer was extracted with 4×20 mL of dichloromethane. The organic layers were combined, dried (Na2SO4), and concentrated under reduced pressure. The residue was purified by preparative thin layer chromatography (silica gel, 2 mm thickness, E. Merck) using 1% methanol in dichloromethane to give 45 mg (0.11 mmol, 27%) of 10 as a colorless thick oil [LC-MS; M+H 412.1].

Workup

  1. concentrationwas concentrated under reduced pressure
  2. additionTo the residue 20 mL of water were added
  3. extractionThe aqueous layer was extracted with 4×20 mL of dichloromethane
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by preparative thin layer chromatography (silica gel, 2 mm thickness, E. Merck)

Sources & evidence

ORD record
ord-dcb0178075d645d89e054b466316e6db
Source dataset
uspto-grants-2008_09
Patent number
US07420043B2

Reaction notes

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