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

HRID 1880010Notes

Reaction equation

HRID 1880010 reaction equation
Br[C:2]1[CH:15]=[N:14][C:5]2[NH:6][CH2:7][CH2:8][C:9](=[O:13])[N:10]([CH3:12])[CH2:11][C:4]=2[CH:3]=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>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:12][N:10]1[C:9](=[O:13])[CH2:8][CH2:7][NH:6][C:5]2[N:14]=[CH:15][C:2](/[CH:18]=[CH:17]/[C:16]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:3][C:4]=2[CH2:11]1

Participants

7

Reactant 4

HCID 15458tert-Butyl acrylateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 593328748-bromo-5-methyl-2,3,5,6-tetrahydropyrido[2,3-b][1,5]diazocin-4(1H)-one

Product 1

HCID 59332864(E)-tert-butyl 3-(5-methyl-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
110 °C

Procedure

A suspension of 8-bromo-5-methyl-2,3,5,6-tetrahydropyrido[2,3-b][1,5]diazocin-4(1H)-one (670 mg, 2.48 mmol), tert-butyl acrylate (1.8 mL, 12.4 mmol) and (i-Pr)2EtN (1.3 mL, 7.44 mmol) in 30 mL of DMF:Propionitriole (4:1) was de-oxygenated with Ar for 30 min. The mixture was treated with Pd(OAc)2 (19.4 mg, 0.09 mmol) and P(o-tol)3 (51.7 mg, 0.18 mmol) then heated to 110° C. for 16 h. The hot mixture was filtered through a pad of celite. The filtrate was diluted with 100 mL H2O then extracted with 2×100 mL ethyl acetate. The resulting brown solid was triturated with a solution of hexanes:ethyl acetate (4:1) followed by filtration to yield the brown solid product. Yield 391 mg (50%); 1H NMR (400 MHz, CDCl3) δ 8.17 (s, 1H), 7.51 (s, 1H), 7.49 (d, J=16.4 Hz, 1H), 6.26 (d, J=16.0 Hz, 1H), 5.22 (bm, 1H), 4.55 (s, 2H), 3.66 (q, J=7.2 Hz, 2H), 3.07 (t, J=7.2 Hz, 2H), 2.81 (s, 3H), 1.55 (s, 9H); ESI MS m/z 318 [C17H23N3O3+H]+

Workup

  1. filtrationThe hot mixture was filtered through a pad of celite
  2. additionThe filtrate was diluted with 100 mL H2O
  3. extractionthen extracted with 2×100 mL ethyl acetate
  4. customThe resulting brown solid was triturated with a solution of hexanes:ethyl acetate (4:1)
  5. filtrationfollowed by filtration
  6. customto yield the brown solid product

Sources & evidence

ORD record
ord-9aa34114720f439bb7073d9383a8bb59
Source dataset
uspto-grants-2012_11
Patent number
US08318720B2

Reaction notes

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