Cesium carbonate → HCID 66697234, compound

HRID 2096748Notes

Reaction equation

HRID 2096748 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:27])[C:9]([C:15]2[CH:16]=[CH:17][C:18]3[O:23][CH2:22][C:21](=[O:24])[N:20]([CH3:25])[C:19]=3[CH:26]=2)([OH:14])[C:10]([F:13])([F:12])[F:11])=[C:4]([Cl:28])[CH:3]=1.[CH3:29][O:30][C:31](=[O:40])[CH2:32][C:33]1[CH:38]=[CH:37][C:36]([OH:39])=[CH:35][CH:34]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl.CN(C)CC(O)=O>O1CCOCC1.[Cu]I.O>[CH3:29][O:30][C:31](=[O:40])[CH2:32][C:33]1[CH:38]=[CH:37][C:36]([O:39][C:2]2[CH:7]=[CH:6][C:5]([CH:8]([CH3:27])[C:9]([OH:14])([C:15]3[CH:16]=[CH:17][C:18]4[O:23][CH2:22][C:21](=[O:24])[N:20]([CH3:25])[C:19]=4[CH:26]=3)[C:10]([F:13])([F:12])[F:11])=[C:4]([Cl:28])[CH:3]=2)=[CH:35][CH:34]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 75605N,N-Dimethylglycine hydrochlorideHCID 518900Benzeneacetic acid, 4-hydroxy-, methyl esterHCID 666971866-[2-(4-Bromo-2-chloro-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-4-methyl-4H-benzo[1,4]oxazin-3-one

Product 1

HCID 66697234HCID 66697234, compoundYield 39%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A suspension of 6-[2-(4-bromo-2-chloro-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-4-methyl-4H-benzo[1,4]oxazin-3-one (Example 22, step 3, 50 mg), methyl-4-hydroxyphenylacetate (26 mg), cesium carbonate (68 mg), copper(I)iodide (2 mg) and N,N-dimethylglycine hydrochloride (4.5 mg) in dioxane (0.5 ml) was heated to 120° C. for 10 min under microwave conditions. The reaction was not finished. The reaction mixture was placed in a heating bath and stirred at 70° C. for 16 h and at 90° C. for 4 h. After cooling to room temperature, water was added and the mixture was extracted with EtOAc. The organic phase was washed with water, filtered and concentrated to dryness. The product was purified by chromatography (SiO2, cyclohexane/EtOAc 1:0=>0:1) to give the title compound (23 mg) as an off-white solid. MS (m/e)=564 [M+H+].

Workup

  1. customThe reaction mixture was placed in a heating bath
  2. temperatureAfter cooling to room temperature
  3. extractionthe mixture was extracted with EtOAc
  4. washThe organic phase was washed with water
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customThe product was purified by chromatography (SiO2, cyclohexane/EtOAc 1:0=>0:1)

Sources & evidence

ORD record
ord-bda5cfcfff3b4b0b9b465e7e4decb0c0
Source dataset
uspto-grants-2013_05
Patent number
US08450313B2

Reaction notes

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