Methane → 6'-(5-Methylpyridin-3-yl)trispiro[cyclobutane-1,2'-chromene-4',4''-[1,3]oxazole-3',3'''-oxetan]-2''-amine

HRID 873758Notes

Reaction equation

HRID 873758 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:17]3([CH2:21][O:20][C:19]([N:22](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)=[N:18]3)[C:13]3([CH2:16][O:15][CH2:14]3)[C:9]3([CH2:12][CH2:11][CH2:10]3)[O:8][C:5]2=[CH:6][CH:7]=1.[CH3:37][C:38]1[CH:39]=[C:40](B(O)O)[CH:41]=[N:42][CH:43]=1.C([O-])([O-])=O.[Na+].[Na+].C>O1CCOCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:37][C:38]1[CH:39]=[C:40]([C:2]2[CH:3]=[C:4]3[C:17]4([CH2:21][O:20][C:19]([NH2:22])=[N:18]4)[C:13]4([CH2:14][O:15][CH2:16]4)[C:9]4([CH2:12][CH2:11][CH2:10]4)[O:8][C:5]3=[CH:6][CH:7]=2)[CH:41]=[N:42][CH:43]=1

Participants

7

Reactant 4

HCID 297MethaneHCID 10340Sodium CarbonateHCID 27627085-Methylpyridine-3-boronic acidHCID 86724300Di-tert-butyl (6'-bromotrispiro[cyclobutane-1,2'-chromene-4',4''-[1,3]oxazole-3',3'''-oxetan]-2''-yl)imidodicarbonate

Product 1

HCID 900251476'-(5-Methylpyridin-3-yl)trispiro[cyclobutane-1,2'-chromene-4',4''-[1,3]oxazole-3',3'''-oxetan]-2''-amineYield 75.3%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

A mixture of di-tert-butyl (6′-bromotrispiro[cyclobutane-1,2′-chromene-4′,4″-[1,3]oxazole-3′,3′″-oxetan]-2″-yl)imidodicarbonate (300 mg, 0.531 mmol), 5-methylpyridine-3-boronic acid (145 mg, 1.06 mmol), bis(triphenylphosphine)palladium(II) dichloride (37 mg, 0.053 mmol) and Na2CO3 (169 mg, 1.59 mmol) in dioxane-H2O (4:1, 6.0 mL) was stirred for 1 hour at 100° C. To the mixture was added charcoal and the mixture was stirred for 10 minutes at 50° C. The mixture was filtered through celite pad (eluted with EtOAc) and the filtrate was washed with H2O and brine. The organic layer was dried over MgSO4 and filtered, and the filtrate was concentrated under reduced pressure. To the residue were added toluene (3.0 mL) and silica gel (neutral; 900 mg), and the mixture was stirred for 3 hours at 120° C. After concentration of the reaction mixture at reduced pressure, the residue was purified with column chromatography on silica gel (CHCl3-EtOH, a linear gradient of EtOH from 0 to 20%) to afford 6′-(5-methylpyridin-3-yl)trispiro[cyclobutane-1,2′-chromene-4′,4″-[1,3]oxazole-3′,3′″-oxetan]-2″-amine (151 mg).

Workup

  1. stirringthe mixture was stirred for 10 minutes at 50° C
  2. filtrationThe mixture was filtered through celite pad (eluted with EtOAc)
  3. washthe filtrate was washed with H2O and brine
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. additionTo the residue were added toluene (3.0 mL) and silica gel (neutral; 900 mg)
  8. stirringthe mixture was stirred for 3 hours at 120° C
  9. customAfter concentration of the reaction mixture at reduced pressure, the residue was purified with column chromatography on silica gel (CHCl3-EtOH

Sources & evidence

ORD record
ord-e40df0589ab94cd3bd41faa97fc3c0f1
Source dataset
uspto-grants-2015_03
Patent number
US08975415B2

Reaction notes

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