Binap, (A+-)- → HCID 68965888, compound

HRID 2220226Notes

Reaction equation

HRID 2220226 reaction equation
BrC1C=CC(CN)=C(COC2C=CC(Cl)=CC=2I)C=1.[Br:20][C:21]1[CH:22]=[CH:23][C:24]([CH2:29][O:30][C:31]2[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][C:32]=2I)=[C:25]([CH:28]=1)[CH2:26][NH2:27].O(C(C)(C)C)[Na].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=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]>[Br:20][C:21]1[CH:22]=[CH:23][C:24]2[CH2:29][O:30][C:31]3[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][C:32]=3[NH:27][CH2:26][C:25]=2[CH:28]=1

Participants

7

Reactant 4

HCID 634876Binap, (A+-)-HCID 59772460HCID 59772460, compoundHCID 68893758HCID 68893758, compoundHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 68965888HCID 68965888, compoundYield 20.5%

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
95 °C

Procedure

To stirred mixture of 4-Bromo-2-(4-chloro-2-iodo-phenoxymethyl)-benzylamine Example 347D (25.9 mg, 57.2 μmol), NaO-t-Bu (18.1 mg, 0.19 mmol), and BINAP (14.3 mg, 22.9 μmol) in anhydrous toluene (0.4 mL) under argon was added Pd(dba)2 (6.60 mg, 11.4 umol). This reaction mixture in a sealed tube was heated at 95° C. for 75 min, cooled to room temperature and concentrated in vacuo. This was purified by a Shimadzu auto prep HPLC, employing 0% 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 3.8 mg of 9-Bromo-2-chloro-11,12-dihydro-6H-5-oxa-12-aza-dibenzo[a,e]cyclooctene in 20% yield. HPLC Rt=3.67 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=324.

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated in vacuo
  3. customThis was purified by a Shimadzu auto prep HPLC
  4. wash0% to 100% 10 min gradient elution
  5. washwith 0.1% TFA in MeOH-water solvent system, 220 nM detection, 20 mL/min elution with a YMC ODS

Sources & evidence

ORD record
ord-07cc4925f90141469d80c60ad510216d
Source dataset
uspto-grants-2008_08
Patent number
US07417040B2

Reaction notes

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