Ammonium Hydroxide → HCID 46205771, compound

HRID 2366482Notes

Reaction equation

HRID 2366482 reaction equation
[C:1](N1CCCC1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C1[CH2:22][C@H:21]2N(C[C@H:18]3[C@@H:25]4[CH2:26][CH2:27][CH2:28][CH2:29]N4[CH2:23][C@@H:20]2[CH2:19]3)CC1.C([Li])(CC)C.C(P)(C)(C)C.[F:40][B-](F)(F)F.[H+].[OH-:46].[NH4+:47].C[O:49][C:50](C)(C)C>[Cl-].[Zn+2].[Cl-].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:40][C:21]1[CH:22]=[C:25]([C@H:26]2[CH2:27][CH2:28][CH2:29][N:47]2[C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[CH:18]=[CH:19][C:20]=1[C:23]([O:49][CH3:50])=[O:46]

Participants

9

Reactant 6

HCID 14923Ammonium HydroxideHCID 15413tert-Butyl methyl etherHCID 643455N-Boc-pyrrolidineHCID 644020SparteineHCID 131730108HCID 131730108, compoundHCID 178418400CID 53628100

Product 1

HCID 46205771HCID 46205771, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 3007855ZincchlorideCatalyst

Procedure

To a solution of N-BOC-pyrrolidine (3.0 mL, 17.1 mmol) and (−)-sparteine (3.9 mL, 17.1 mmol) in tert-butyl methyl ether (36 mL) at −78° C. was added sec-butyl lithium (1.4 M solution in cyclohexane, 12.21 mL, 17.1 mmol) and the mixture stirred at <−70° C. for 3 hours. A solution of zinc (II) chloride (1M solution in diethyl ether, 10.2 mL, 10.2 mmol) was added, the mixture stirred at −78° C. for 30 minutes and then warmed to ambient temperature. The mixture was stirred for 30 minutes and EXAMPLE 50A (3.32 g, 14.25 mmol), t-butylphosphine-tetrafluoroboric acid (249 mg, 0.855 mmol) and palladium (II) acetate (153 mg, 0.69 mmol) were added and the mixture stirred at ambient temperature overnight. Concentrated ammonium hydroxide (1 mL) was added and the mixture stirred at ambient temperature for 30 minutes. Insoluble material was filtered through Celite and washed with ethyl acetate. The filtrate was washed with 0.5 M hydrochloric acid and water and concentrated. The residue was purified by flash chromatography on silica gel, using a gradient of 10-30% ethyl acetate in hexane to give the title compound (2.66 g).

Workup

  1. stirringthe mixture stirred at −78° C. for 30 minutes
  2. stirringThe mixture was stirred for 30 minutes
  3. stirringthe mixture stirred at ambient temperature overnight
  4. stirringthe mixture stirred at ambient temperature for 30 minutes
  5. filtrationInsoluble material was filtered through Celite
  6. washwashed with ethyl acetate
  7. washThe filtrate was washed with 0.5 M hydrochloric acid and water
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-49ef5b86b72e40d584d240a1c1102dd7
Source dataset
uspto-grants-2014_04
Patent number
US08697736B2

Reaction notes

Loading…