Tri-o-tolylphosphine → HCID 16659660, compound

HRID 1362295Notes

Reaction equation

HRID 1362295 reaction equation
[CH3:1][N:2]([CH2:7][C:8]1[O:9][C:10]2[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=2[C:12]=1[CH3:13])[C:3](=[O:6])[CH:4]=[CH2:5].C(N(C(C)C)CC)(C)C.Br[C:28]1[CH:29]=[N:30][C:31]2[NH:40][C:39](=[O:41])[C@H:38]3[N:34]([CH2:35][CH2:36][CH2:37]3)[CH2:33][C:32]=2[CH:42]=1.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)CC.CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:1][N:2]([CH2:7][C:8]1[O:9][C:10]2[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=2[C:12]=1[CH3:13])[C:3](=[O:6])/[CH:4]=[CH:5]/[C:28]1[CH:29]=[N:30][C:31]2[NH:40][C:39](=[O:41])[C@H:38]3[N:34]([CH2:35][CH2:36][CH2:37]3)[CH2:33][C:32]=2[CH:42]=1

Participants

8

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 57742026HCID 57742026, compoundHCID 57742103N-methyl-N-(3-methylbenzofuran-2-ylmethyl)acrylamide

Product 1

HCID 16659660HCID 16659660, compoundYield 82%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 7854PropionitrileSolvent

Procedure

A solution of N-methyl-N-(3-methylbenzofuran-2-ylmethyl)acrylamide (0.210 g, 0.920 mmol) in propionitrile (3 mL) and DMF (0.65 mL) was deoxygenated with Ar for 20 min. The solution was treated with diisopropylethylamine (0.24 mL, 1.4 mmol) and (S)-6-bromo-1,2,3,4,9,10a-hexahydro-3a,8,9-triazabenzo[f]azulen-10-one (0.200 g, 0.708 mmol). The solution was deoxygenated with Ar for 20 min. Pd(OAc)2 (0.015 g, 0.070 mmol) and P(o-tol)3 (0.067 g, 0.14 mmol) were then added and the solution was deoxygenated with Ar for 20 min. The solution was heated to reflux for 18 h, then allowed to cool. The solution was diluted with CH2Cl2 (50 mL) and was washed with H2O (3×100 mL). The combined organics were washed with brine (2×100 mL), dried (Na2SO4) and concentrated. Purification by column chromatography (silica gel, CH2Cl2/MeOH, 98:2) gave the title compound (0.25 g, 77%) as a glassy yellow solid and as a mixture of amide rotamers: 1H NMR (300 MHz, CDCl3) δ 8.74 (s, 1H), 8.60-8.50 (m, 1H), 7.75-7.67 (m, 2H), 7.49-7.48 (m, 1H), 7.42-7.40 (m, 1H), 7.28-7.16 (m, 3H), 4.83-4.71 (m, 2H), 3.99-3.82 (m, 2H), 3.59-2.57 (m, 1H), 3.23-3.08 (m, 3H), 2.89-2.86 (m, 2H), 2.53-2.44 (m, 1H), 2.31-2.30 (m, 3H), 2.04-1.68 (m, 3H).

Workup

  1. customThe solution was deoxygenated with Ar for 20 min
  2. customthe solution was deoxygenated with Ar for 20 min
  3. temperatureThe solution was heated
  4. temperatureto reflux for 18 h
  5. temperatureto cool
  6. additionThe solution was diluted with CH2Cl2 (50 mL)
  7. washwas washed with H2O (3×100 mL)
  8. washThe combined organics were washed with brine (2×100 mL)
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated
  11. customPurification by column chromatography (silica gel, CH2Cl2/MeOH, 98:2)

Sources & evidence

ORD record
ord-0345da5ca349408381015f694816e7d4
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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