Binap, (A+-)- → 2-Chloro-11,12-dihydro-6H-5-oxa-11-aza-dibenzo[a,e]cyclooctene

HRID 2220230Notes

Reaction equation

HRID 2220230 reaction equation
Br[C:2]1[CH:18]=[CH:17][CH:16]=[CH:15][C:3]=1[CH2:4][O:5][C:6]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][C:7]=1[CH2:8][NH2:9].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.O(C(C)(C)C)[Na]>C1(C)C=CC=CC=1.C([O-])(O)=O.[Na+].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]>[Cl:14][C:11]1[CH:12]=[CH:13][C:6]2[O:5][CH2:4][C:3]3[CH:15]=[CH:16][CH:17]=[CH:18][C:2]=3[NH:9][CH2:8][C:7]=2[CH:10]=1

Participants

7

Reactant 3

HCID 634876Binap, (A+-)-HCID 59772401HCID 59772401, compound2×HCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 597723972-Chloro-11,12-dihydro-6H-5-oxa-11-aza-dibenzo[a,e]cycloocteneYield 51%

Reagents, catalysts & solvents 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 1140TolueneSolventHCID 516892Sodium BicarbonateSolvent2×

Conditions

Temperature
120 °C

Procedure

To a stirred mixture of 2-(2-Bromo-benzyloxy)-5-chloro-benzylamine Example 348B (112 mg, 0.34 mmol), BINAP (43.1 mg, 69.3 mmol), and NaO-t-Bu (100 mg, 34.7 mmol) in anhydrous toluene (3.0 mL) under argon was added Pd(dba)2 (20.0 mg, 1.04 mmol). This mixture was heated at 120° C. in a sealed tube for 1 hour and then cooled to room temperature. The mixture was diluted with saturated NaHCO3 solution (40 mL), further saturated with solid NaHCO3, and then extracted with EtOAc (2×60 mL). The combined EtOAc extracts were dried (MgSO4), filtered and concentrated in vacuo. The crude was purified by a ISCO auto CombiFlash with a RediSep 10 g column, eluted with CH2Cl2-EtOAc, detected at 220 nM to give 44 mg of desired 2-Chloro-11,12-dihydro-6H-5-oxa-11-aza-dibenzo[a,e]cyclooctene Example 348C in 51% yield. HPLC Rt=2.05 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=246

Workup

  1. temperaturecooled to room temperature
  2. extractionextracted with EtOAc (2×60 mL)
  3. dry with materialThe combined EtOAc extracts were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude was purified by a ISCO auto CombiFlash with a RediSep 10 g column
  7. washeluted with CH2Cl2-EtOAc

Sources & evidence

ORD record
ord-d277bf929a604fd5b638f7063f8550f8
Source dataset
uspto-grants-2008_08
Patent number
US07417040B2

Reaction notes

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