Sodium Carbonate → 3-(1-(4-(2-Methoxypyridin-4-yl)phenyl)cyclopropyl)-6-(2-methylallyl)-6-phenyl-1,3-oxazinan-2-one

HRID 1422655Notes

Reaction equation

HRID 1422655 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([N:11]3[CH2:16][CH2:15][C:14]([CH2:23][C:24]([CH3:26])=[CH2:25])([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[O:13][C:12]3=[O:27])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[CH3:28][O:29][C:30]1[CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:33]=[CH:32][N:31]=1.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1>[CH3:28][O:29][C:30]1[CH:35]=[C:34]([C:2]2[CH:7]=[CH:6][C:5]([C:8]3([N:11]4[CH2:16][CH2:15][C:14]([CH2:23][C:24]([CH3:26])=[CH2:25])([C:17]5[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=5)[O:13][C:12]4=[O:27])[CH2:10][CH2:9]3)=[CH:4][CH:3]=2)[CH:33]=[CH:32][N:31]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 447548622-Methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 668695453-(1-(4-Bromophenyl)cyclopropyl)-6-(2-methylallyl)-6-phenyl-1,3-oxazinan-2-one

Product 1

HCID 668695683-(1-(4-(2-Methoxypyridin-4-yl)phenyl)cyclopropyl)-6-(2-methylallyl)-6-phenyl-1,3-oxazinan-2-oneYield 75%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

3-(1-(4-bromophenyl)cyclopropyl)-6-(2-methylallyl)-6-phenyl-1,3-oxazinan-2-one (33 mg, 0.078 mmol), 2-methoxypyridine-4-boronic acid pinacol ester (27 mg, 1.5 equiv), Pd(dppf)Cl2 (6 mg, 10% mol), 2M aq Na2CO3 (1 mL), 1,4-dioxane (2.5 mL) were mixed in a tube for microwave oven. The tube was evacuated and refilled with nitrogen gas (3×) and heated in the microwave oven for 120 min at 130° C. LC-MS found the reaction was complete. The mixture was diluted with EtOAc (10 mL), washed with water (4 mL) and brine (3 mL), and dried over Na2SO4. After filtration and concentration, the residue was purified by chromatography on a 4-g silica gel column, eluted with a 10˜50% EtOAc in hexanes gradient, to afford 3-(1-(4-(2-methoxypyridin-4-yl)phenyl)cyclopropyl)-6-(2-methylallyl)-6-phenyl-1,3-oxazinan-2-one (26.5 mg, 75%) as a clear oil.

Workup

  1. customThe tube was evacuated
  2. additionrefilled with nitrogen gas (3×)
  3. additionThe mixture was diluted with EtOAc (10 mL)
  4. washwashed with water (4 mL) and brine (3 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationAfter filtration and concentration
  7. customthe residue was purified by chromatography on a 4-g silica gel column
  8. washeluted with a 10˜50% EtOAc in hexanes gradient

Sources & evidence

ORD record
ord-b34d940d1af94619b44d91a6975d9b09
Source dataset
uspto-grants-2015_01
Patent number
US08927539B2

Reaction notes

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