Sodium Carbonate → HCID 67814402, compound

HRID 2401423Notes

Reaction equation

HRID 2401423 reaction equation
Cl[C:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[C:6]2[C:13]([CH3:16])=[N:14][O:15][C:5]=2[C@H:4]([CH2:17][C:18]([O:20][CH3:21])=[O:19])[N:3]=1.[Cl:22][C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1.C(=O)([O-])[O-].[Na+].[Na+]>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>[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([C:2]2[C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=3[C:6]3[C:13]([CH3:16])=[N:14][O:15][C:5]=3[C@H:4]([CH2:17][C:18]([O:20][CH3:21])=[O:19])[N:3]=2)=[CH:25][CH:24]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 742994-Chlorophenylboronic acidHCID 67814789HCID 67814789, compound

Product 1

HCID 67814402HCID 67814402, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To a 100 mL round bottom flask containing methyl 2-((4S)-6-chloro-1-methyl-4H-benzo[c]isoxazolo[4,5-e]azepin-4-yl)acetate (0.4701 g, 1.543 mmol) was added Pd(PPh3)4 (0.095 g, 0.082 mmol) and 4-chlorophenylboronic acid (0.393 g, 2.51 mmol). The flask was evacuated and purged with N2 (g) (3×), followed by addition of toluene (10 mL) and another cycle of evacuation and purging with N2 (g). To the heterogeneous mixture was added aqueous sodium carbonate (2.4 mL, 4.80 mmol, 2 M) in one portion and the flask was heated to 80° C. After ˜30 min, the reaction mixture was cooled to room temperature and diluted with water. The aqueous layer was extracted with EtOAc (3×), dried over Na2SO4, and concentrated to give a dark orange oil. The oil was purified on Biotage system (5% EtOAc:95% Hexanes to 35% EtOAc:65% Hexanes, then isocratic 35% EtOAc:65% Hexanes). The product methyl 2-((4S)-6-(4-chlorophenyl)-1-methyl-4H-benzo[c]isoxazolo[4,5-e]azepin-4-yl)acetate (0.444 g, 1.166 mmol, 76% yield) was obtained as yellow foam after drying. LC/MS m/z 381 [M+H]+.

Workup

  1. customThe flask was evacuated
  2. custompurged with N2 (g) (3×)
  3. additionfollowed by addition of toluene (10 mL)
  4. customanother cycle of evacuation and purging with N2 (g)
  5. temperaturethe reaction mixture was cooled to room temperature
  6. extractionThe aqueous layer was extracted with EtOAc (3×)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customto give a dark orange oil
  10. customThe oil was purified on Biotage system (5% EtOAc

Sources & evidence

ORD record
ord-17911e8bf24e432eb4da18a488e80952
Source dataset
uspto-grants-2014_08
Patent number
US08796261B2

Reaction notes

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