Potassium Phosphate, Tribasic → HCID 66982637, compound

HRID 516245Notes

Reaction equation

HRID 516245 reaction equation
[CH3:1][CH:2]1[C:8]2[CH:9]=[C:10]3[NH:16][CH2:15][CH2:14][O:13][C:11]3=[CH:12][C:7]=2[CH2:6][CH2:5][N:4]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:3]1.BrN1[C:29](=O)[CH2:28][CH2:27]C1=O.C1(OB(O)O)CC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1>[CH:27]1([C:9]2[C:8]3[CH:2]([CH3:1])[CH2:3][N:4]([C:17]([O:19][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:18])[CH2:5][CH2:6][C:7]=3[CH:12]=[C:11]3[O:13][CH2:14][CH2:15][NH:16][C:10]=23)[CH2:28][CH2:29]1

Participants

10

Reactant 5

HCID 62657Potassium Phosphate, TribasicHCID 67184N-bromobutanimideHCID 75806TricyclohexylphosphineHCID 66812283HCID 66812283, compoundHCID 66982120HCID 66982120, compound

Product 1

HCID 66982637HCID 66982637, compoundYield 47.8%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 704 mg of t-butyl 6-methyl-3,4,6,7,9,10-hexahydro[1,4]oxazino[2,3-h][3]benzazepine-8(2H)-carboxylate in 15 ml of dichloromethane was added portionwise 438 mg of N-bromosuccinimide under ice-cooling, followed by stirring for 30 minutes. The reaction mixture was concentrated under reduced pressure and the residue was purified by silica gel chromatography (elution solvent: HEX-EtOAc) to obtain 446 mg of a pale yellow foamed substance. To a mixture of 445 mg of the resulting compound, 144 mg of cyclopropylboric acid, 724 mg of potassium phosphate, 65 mg of tricyclohexylphosphine, and 28 mg of palladium(II) acetate were added 10 ml of toluene and 0.5 ml of water, followed by stirring at 110° C. for 12 hours. The reaction mixture was filtered through celite and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (elution solvent: HEX-EtOAc) to obtain 379 mg of t-butyl 5-cyclopropyl-6-methyl-3,4,6,7,9,10-hexahydro[1,4]oxazino[2,3-h][3]benzazepine-8(2H)-carboxylate as a pale brown foamed substance.

Workup

  1. temperaturecooling
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customthe residue was purified by silica gel chromatography (elution solvent: HEX-EtOAc)
  4. customto obtain 446 mg of a pale yellow foamed substance
  5. stirringby stirring at 110° C. for 12 hours
  6. filtrationThe reaction mixture was filtered through celite
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe residue was purified by silica gel chromatography (elution solvent: HEX-EtOAc)

Sources & evidence

ORD record
ord-6548d861d9854ac398f62fb565bf6cdc
Source dataset
uspto-grants-2015_08
Patent number
US09108977B2

Reaction notes

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