Binap, (A+-)- → HCID 86721996, compound

HRID 574176Notes

Reaction equation

HRID 574176 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12](Br)=[CH:11][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:16]([N:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][CH:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)=[O:26])[CH2:21][CH2:20]1)([CH3:18])[CH3:17].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.CC([O-])(C)C.[K+]>C1(C)C=CC=CC=1.CC(=O)OCC.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]>[CH:16]([N:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][CH:28]2[CH2:29][CH2:30][N:31]([C:12]3[CH:11]=[N:10][C:9]([O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[CH:14][CH:13]=3)[CH2:32][CH2:33]2)=[O:26])[CH2:21][CH2:20]1)([CH3:18])[CH3:17]

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 111081912-Benzyloxy-5-bromopyridineHCID 23665647Potassium tert-butoxideHCID 86721997HCID 86721997, compound

Product 1

HCID 86721996HCID 86721996, compoundYield 20.4%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 2-(benzyloxy)-5-bromopyridine (1.5 g, 5.6 mmol), piperidin-4-yl 4-isopropylpiperazine-1-carboxylate (2.15 g, 8.4 mmol) in toluene (30 mL) was added Pd2(dba)3 (1.57 g, 2.2 mmol), BINAP (2.79 g, 4.4 mmol) and t-BuOK (3.78 g, 33.8 mmol). The reaction was stirred under the microwave irradiation at 120° C. for 20 min. The mixture was diluted with EA (100 mL) and washed with water (3×50 mL). The organic phase was separated, dried and concentrated to dryness. The residue was taken into dilute HCl (pH=1, 100 mL) and the mixture was extracted with DCM (3×100 mL) to remove impurities. The aqueous phase was made basic (pH=9-10) with solid Na2CO3 and extracted with DCM (3×100 mL). The combined organic layers were dried, concentrated and purified by silica gel chromatography (EA/MeOH=50/1) to give the title compound as a white solid (500 mg, 20%). [LCMS: Rt=2.09 mim, m/z 439.3 (M+H)+].

Workup

  1. washwashed with water (3×50 mL)
  2. customThe organic phase was separated
  3. customdried
  4. concentrationconcentrated to dryness
  5. extractionthe mixture was extracted with DCM (3×100 mL)
  6. customto remove impurities
  7. extractionextracted with DCM (3×100 mL)
  8. customThe combined organic layers were dried
  9. concentrationconcentrated
  10. custompurified by silica gel chromatography (EA/MeOH=50/1)

Sources & evidence

ORD record
ord-62caa65bcfea469b88dd0d90e171f78a
Source dataset
uspto-grants-2015_05
Patent number
US09034874B2

Reaction notes

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