Methane → (E)-tert-butyl 3-(4-oxo-1,2,3,4,5,6-hexahydropyrido[2,3-b][1,5]diazocin-8-yl)acrylate

HRID 1880005Notes

Reaction equation

HRID 1880005 reaction equation
Br.Br[C:3]1[CH:15]=[N:14][C:6]2[NH:7][CH2:8][CH2:9][C:10](=[O:13])[NH:11][CH2:12][C:5]=2[CH:4]=1.[C:16]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])(=[O:19])[CH:17]=[CH2:18].C(N(C(C)C)C(C)C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C>CC([O-])=O.CC([O-])=O.[Pd+2].CN(C=O)C>[O:13]=[C:10]1[CH2:9][CH2:8][NH:7][C:6]2[N:14]=[CH:15][C:3](/[CH:18]=[CH:17]/[C:16]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:4][C:5]=2[CH2:12][NH:11]1

Participants

8

Reactant 5

HCID 297MethaneHCID 15458tert-Butyl acrylateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 684127008-bromo-2,3,5,6-tetrahydropyrido[2,3-b][1,5]diazocin-4(1H)-one hydrobromide

Product 1

HCID 59332845(E)-tert-butyl 3-(4-oxo-1,2,3,4,5,6-hexahydropyrido[2,3-b][1,5]diazocin-8-yl)acrylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A round bottom flask was charged with 8-bromo-2,3,5,6-tetrahydropyrido[2,3-b][1,5]diazocin-4(1H)-one hydrobromide (0.5 g, 1.48 mmol), tert-butyl acrylate (1.1 mL, 7.42 mmol), and (i-Pr)2EtN (1.5 mL, 8.88 mmol) followed by 15 mL DMF. The solution was de-oxygenated with argon for 20 minutes. The mixture was treated with Pd(OAc)2 (17 mg, 0.07 mmol) and P(o-tol)3 (45 mg, 0.15 mmol) then heated to 100° C. for 18 hours (overnight). After cooling, the dark mixture was treated with activated charcoal (100 mg) and filtered through celite. The filtrate was partitioned between 150 mL CH2Cl2 and 50 mL H2O in a separatory funnel. The organic layer was separated and treated with 3×50 mL saturated sodium chloride solution then dried over MgSO4 and concentrated to give a brown residue. This residue was triturated with 20% Et2O:hexanes to give a solid. The solid was collected and subjected to flash chromatography on silica gel using 5% MeOH:95% CH2Cl2. Yield: 200 mg (44.5%); 1H-NMR (400 MHz, DMSO-d6) δ 8.12 (d, 1H, J=2.4 Hz), 7.74 (d, 1H, J=2.4 Hz), 7.44 (m, 1H), 7.41 (d, 1H, J=16.0 Hz), 6.94 (t, 1H, J=6.4 Hz), 6.29 (d, 1H, J=15.6 Hz), 4.46 (d, 2H, J=7.6 Hz), 3.61 (m, 2H), 2.73 (t, 2H, J=7.2 Hz), 1.46 (s, 9H); ESI MS m/z 304 [C16H21N3O3+H]+

Workup

  1. temperatureAfter cooling
  2. filtrationfiltered through celite
  3. customThe filtrate was partitioned between 150 mL CH2Cl2 and 50 mL H2O in a separatory funnel
  4. customThe organic layer was separated
  5. additiontreated with 3×50 mL saturated sodium chloride solution
  6. dry with materialthen dried over MgSO4
  7. concentrationconcentrated
  8. customto give a brown residue
  9. customThis residue was triturated with 20% Et2O
  10. customhexanes to give a solid
  11. customThe solid was collected

Sources & evidence

ORD record
ord-86c9c9156c5644d0857624390dc570db
Source dataset
uspto-grants-2012_11
Patent number
US08318720B2

Reaction notes

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