Hydrochloric Acid → HCID 11233574, compound

HRID 1437022Notes

Reaction equation

HRID 1437022 reaction equation
Br[C:2]1[CH:17]=[CH:16][C:5]2[O:6][C:7]3[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=3[C:9](=O)[NH:10][C:4]=2[CH:3]=1.[C:18]1(B(O)O)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C([O-])([O-])=O.[K+].[K+].[NH:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1.Cl>C1(C)C=CC=CC=1.CCO.O.CCOC(C)=O.O1CCOCC1.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[Ti](Cl)(Cl)Cl>[C:18]1([C:2]2[CH:17]=[CH:16][C:5]3[O:6][C:7]4[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=4[C:9]([N:33]4[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]4)=[N:10][C:4]=3[CH:3]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

11

Reactant 5

HCID 313Hydrochloric AcidHCID 4837PiperazineHCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 57485433HCID 57485433, compound

Product 1

HCID 11233574HCID 11233574, compoundYield 37.5%

Reagents, catalysts & solvents 5

HCID 24193Titanium TetrachlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent2×HCID 86587398Ethanol toluene waterSolvent

Conditions

Temperature
140 °C

Procedure

To a mixture of 8-bromo-10H-dibenzo[b,f][1,4]oxazepin-11-one (189JO56) (30 mg, 0.12 mmol), benzene boronic acid (18 mg, 0.15 mmol) and K2CO3 (34 mg, 0.24 mmol) in deoxygenised toluene/EtOH/H2O (1.5 mL) was added tetrakis(triphenylphosphine)palladium(0) (catalytic amount) and the resulting mixture was heated in a capped tube in a microwave oven (140° C., 15 min). The mixture was diluted with EtOAc, washed with saturated aqueous NaHCO3-solution, dried (Na2SO4) and concentrated to give crude 8-phenyl lactam. A mixture of the intermediate 8-phenyl lactam in dioxane (1 mL) was added to a mixture of TiCl4 (0.27 mL, 0.27 mmol, 1 M in toluene) and piperazine (0.103 g, 1.2 mmol) in dioxane at 50° C. The resulting mixture was stirred at 100° C. over night and then allowed to obtain room temperature. To the mixture was added aqueous HCl (3 mL, 2 M) and then the aqueous phase was extracted with EtOAc (2×4 mL). To the aqueous phase was added aqueous NaOH (6 mL, 2 M) and the resulting suspension was extracted with EtOAc (3×3 mL). The combined organic phases were applied onto a SCX-2 ion exchange column. The column was washed with MeOH, and then the product was eluted with NH3 (7 N in MeOH) concentrated and purified by HPLC to give 16 mg of the title compound (189JO64). MS (ESI) 356 (MH+). Purity for MH+ (UV/MS) 100/99.

Workup

  1. washwashed with saturated aqueous NaHCO3-solution
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. customto give crude 8-phenyl lactam
  5. customto obtain room temperature
  6. extractionthe aqueous phase was extracted with EtOAc (2×4 mL)
  7. additionTo the aqueous phase was added aqueous NaOH (6 mL, 2 M)
  8. extractionthe resulting suspension was extracted with EtOAc (3×3 mL)
  9. washThe column was washed with MeOH
  10. washthe product was eluted with NH3 (7 N in MeOH)
  11. concentrationconcentrated
  12. custompurified by HPLC

Sources & evidence

ORD record
ord-0e5d0478d21940fe80182aad21fd815b
Source dataset
uspto-grants-2009_11
Patent number
US07622461B2

Reaction notes

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