Sodium Carbonate → (2R,6R,11S)-6,11-Dimethyl-8-(6-methyl-pyridazin-3-yl)-1,2,3,4,5,6-hexahydro-2,6-methano-benzo[d]azocine

HRID 536666Notes

Reaction equation

HRID 536666 reaction equation
C([O-])([O-])=O.[Na+].[Na+].C(OC([N:14]1[CH2:21][CH2:20][C@:19]2([CH3:24])[C@H:22]([CH3:23])[C@H:15]1[CH2:16][C:17]1[CH:28]=[CH:27][C:26](B3OC(C)(C)C(C)(C)O3)=[CH:25][C:18]=12)=O)(C)(C)C.Cl[C:39]1[N:40]=[N:41][C:42]([CH3:45])=[CH:43][CH:44]=1>CN(C)C=O>[CH3:24][C@:19]12[C@H:22]([CH3:23])[C@H:15]([NH:14][CH2:21][CH2:20]1)[CH2:16][C:17]1[CH:28]=[CH:27][C:26]([C:39]3[N:40]=[N:41][C:42]([CH3:45])=[CH:43][CH:44]=3)=[CH:25][C:18]2=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 2272543-Chloro-6-methylpyridazineHCID 58123692(2R,6R,11S)-6,11-dimethyl-8-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,2,5,6-tetrahydro-4H-2,6-methano-benzo[d]azocine-3-carboxylic acid tert-butyl ester

Product 1

HCID 58123610(2R,6R,11S)-6,11-Dimethyl-8-(6-methyl-pyridazin-3-yl)-1,2,3,4,5,6-hexahydro-2,6-methano-benzo[d]azocine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

2 M Aqueous Na2CO3 solution (1.13 mL) is added to a mixture of (2R,6R,11S)-6,11-dimethyl-8-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,2,5,6-tetrahydro-4H-2,6-methano-benzo[d]azocine-3-carboxylic acid tert-butyl ester (483 mg) and 3-chloro-6-methyl-pyridazine (218 mg) in dimethylformamide (2 mL). The resulting mixture is flushed with argon and then 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride dichloromethane complex (73 mg) is added. The mixture is heated to 100° C. and stirred at this temperature overnight. After cooling to room temperature, water is added and the resulting mixture is extracted with ethyl acetate. The combined organic extracts are washed with water and brine and dried (MgSO4). The solvent is removed under reduced pressure and the residue is taken up in CH2Cl2 (3 mL) and treated with F3CCOO2H (0.5 mL) for 1 h. Then, the solution is concentrated and the residue is purified by HPLC on reversed phase (MeCN/H2O/NH3) to afford the title compound.

Workup

  1. customThe resulting mixture is flushed with argon
  2. addition1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride dichloromethane complex (73 mg) is added
  3. temperatureAfter cooling to room temperature
  4. additionwater is added
  5. extractionthe resulting mixture is extracted with ethyl acetate
  6. washThe combined organic extracts are washed with water and brine
  7. dry with materialdried (MgSO4)
  8. customThe solvent is removed under reduced pressure
  9. additiontreated with F3CCOO2H (0.5 mL) for 1 h
  10. concentrationThen, the solution is concentrated
  11. customthe residue is purified by HPLC on reversed phase (MeCN/H2O/NH3)

Sources & evidence

ORD record
ord-ab1ad1f1908049cd85c1c9057cd348cc
Source dataset
uspto-grants-2014_10
Patent number
US08859580B2

Reaction notes

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