Tris(1,1-dimethylethyl)phosphine → 1-(2-Phenyl-6H,12H-5-oxa-11-aza-dibenzo[a,e]cycloocten-11-yl)-ethanone

HRID 2220232Notes

Reaction equation

HRID 2220232 reaction equation
Cl[C:2]1[CH:20]=[CH:19][C:5]2[O:6][CH2:7][C:8]3[CH:18]=[CH:17][CH:16]=[CH:15][C:9]=3[N:10]([C:12](=[O:14])[CH3:13])[CH2:11][C:4]=2[CH:3]=1.[F-].[K+].[C:23]1(OB=O)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:23]1([C:2]2[CH:20]=[CH:19][C:5]3[O:6][CH2:7][C:8]4[CH:18]=[CH:17][CH:16]=[CH:15][C:9]=4[N:10]([C:12](=[O:14])[CH3:13])[CH2:11][C:4]=3[CH:3]=2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

7

Reactant 4

HCID 83681Tris(1,1-dimethylethyl)phosphine3×HCID 522689Potassium FluorideHCID 14438906HCID 14438906, compoundHCID 597724811-(2-Chloro-6H,12H-5-oxa-11-aza-dibenzo[a,e]cycloocten-11-yl)-ethanone

Product 1

HCID 116168791-(2-Phenyl-6H,12H-5-oxa-11-aza-dibenzo[a,e]cycloocten-11-yl)-ethanone

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst3×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred mixture of 1-(2-Chloro-6H,12H-5-oxa-11-aza-dibenzo[a,e]cycloocten-11-yl)-ethanone Example 348D (21.5 mg, 74.7 umol), KF (14.3 mg, 0.25 mmol), phenylboranic acid (10.0 mg, 82.2 umol) and tri-t-butyl phosphine (4.54 mg, 22.4 umol) in dioxane (0.40 mL) under argon was added Pd2(dba)3 (6.84 mg, 7.47 umol). This mixture was heated at 80° C. for 19 hours and cooled to room temperature. To this cooled mixture under argon was added more Pd2 (dba)3 and tri-t-butyl phosphine. This mixture was then heated at 100° C. for 24 h upon which time some more Pd2 (dba)3 and tri-t-butyl phosphine were added. The mixture was heated at 80° C. for another 24 h and cooled to room temperature. This mixture was concentrated in vacuo and purified by a ISCO auto CombiFlash with a RediSep 4 g column, eluted with CH2Cl2-EtOAc, detected at 220 nM to give 4.3 mg of impure 1-(2-Phenyl-6H,12H-5-oxa-11-aza-dibenzo[a,e]cycloocten-11-yl)-ethanone Example 348. This was further purified by a Shimadzu auto prep HPLC, employing 30% to 100% 10 min gradient elution with 0.1% TFA in MeOH-water solvent system, 220 nM detection, 20 mL/min elution with a YMC ODS S5 20×100 mm column to give 3.3 mg of 1-(2-Phenyl-6H,12H-5-oxa-11-aza-dibenzo[a,e]cycloocten-11-yl)-ethanone Example 348 in 13% yield. HPLC Rt=3.53 min (YMC S5 ODS column 4.6×50 mm, 10-90% aqueous methanol over 4 minutes containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm) LC/MS: M+H=330

Workup

  1. temperaturecooled to room temperature
  2. additionwere added
  3. temperatureThe mixture was heated at 80° C. for another 24 h
  4. temperaturecooled to room temperature
  5. concentrationThis mixture was concentrated in vacuo
  6. custompurified by a ISCO auto CombiFlash with a RediSep 4 g column
  7. washeluted with CH2Cl2-EtOAc

Sources & evidence

ORD record
ord-a90c135080eb4afd8391386547115a8f
Source dataset
uspto-grants-2008_08
Patent number
US07417040B2

Reaction notes

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