Potassium Carbonate → 2-(4,4-Dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-pyrrole-1-carboxylic acid tert-butyl ester

HRID 2260975Notes

Reaction equation

HRID 2260975 reaction equation
Br[C:2]1[CH:14]=[CH:13][C:5]2[NH:6][C:7](=[O:12])[O:8][C:9]([CH3:11])([CH3:10])[C:4]=2[CH:3]=1.[C:15]([O:19][C:20]([N:22]1[CH:26]=[CH:25][CH:24]=[C:23]1B(O)O)=[O:21])([CH3:18])([CH3:17])[CH3:16].C(=O)([O-])[O-].[K+].[K+].C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C(O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:15]([O:19][C:20]([N:22]1[CH:26]=[CH:25][CH:24]=[C:23]1[C:2]1[CH:14]=[CH:13][C:5]2[NH:6][C:7](=[O:12])[O:8][C:9]([CH3:11])([CH3:10])[C:4]=2[CH:3]=1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 30630BrofoxineHCID 516892Sodium BicarbonateHCID 27343211-(tert-Butoxycarbonyl)-2-pyrroleboronic Acid

Product 1

HCID 114392892-(4,4-Dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-pyrrole-1-carboxylic acid tert-butyl esterYield 58.4%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one (5.0 g, 20 mmol) and tetrakis(triphenylphosphine)palladium(0) (580 mg, 0.5 mmol) in toluene (200 mL) was stirred under a flow of nitrogen for 25 min. To the solution was added sequentially 1-tert-butoxycarbonylpyrrole-2-boronic acid (8.24 g, 39 mmol) in absolute ethanol (50 mL) and potassium carbonate (5.39 g, 39 mmol) in water (50 mL). The mixture was heated to 80° C. for 16 hours and allowed to cool. The reaction mixture was poured into aqueous saturated sodium bicarbonate solution (200 mL) and extracted with ethyl acetate (3×200 mL). The organic layers were combined, washed with water (200 mL) and brine (100 mL) and dried over magnesium sulfate. The solution was filtered, concentrated in vacuo, and the residue was purified by flash column chromatography on silica gel (30% ethyl acetate/hexane) to give 2-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-pyrrole-1carboxylic acid tert-butyl ester (4.0 g, 58%) as a tan solid, mp 172-173° C.

Workup

  1. temperatureto cool
  2. extractionextracted with ethyl acetate (3×200 mL)
  3. washwashed with water (200 mL) and brine (100 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationThe solution was filtered
  6. concentrationconcentrated in vacuo
  7. customthe residue was purified by flash column chromatography on silica gel (30% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-27d379a7be8040099fcec4e8f9bb0149
Source dataset
uspto-grants-2010_12
Patent number
US07846924B2

Reaction notes

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