tert-Butyl acrylate → (R)-(E)-3-(10-Oxo-2,3,4,9,10,10a-hexahydro-1H-3a,8,9-triaza-benzo[f]azulen-6-yl)acrylic acid tert-butyl ester

HRID 1362062Notes

Reaction equation

HRID 1362062 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]2[NH:14][C:13](=[O:15])[C@@H:12]3[N:8]([CH2:9][CH2:10][CH2:11]3)[CH2:7][C:6]=2[CH:16]=1.[C:17]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])(=[O:20])[CH:18]=[CH2:19].C(N(C(C)C)C(C)C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)CC.CN(C=O)C.C(Cl)Cl.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:22]([O:21][C:17](=[O:20])/[CH:18]=[CH:19]/[C:2]1[CH:3]=[N:4][C:5]2[NH:14][C:13](=[O:15])[C@@H:12]3[N:8]([CH2:9][CH2:10][CH2:11]3)[CH2:7][C:6]=2[CH:16]=1)([CH3:25])([CH3:24])[CH3:23]

Participants

9

Reactant 4

HCID 15458tert-Butyl acrylateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 59456939(R)-6-bromo-1,2,3,4,9,10a-hexahydro-3a,8,9-triazabenzo[f]azulen-10-one

Product 1

HCID 59456975(R)-(E)-3-(10-Oxo-2,3,4,9,10,10a-hexahydro-1H-3a,8,9-triaza-benzo[f]azulen-6-yl)acrylic acid tert-butyl esterYield 56%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 7854PropionitrileSolvent

Procedure

A suspension of (R)-6-bromo-1,2,3,4,9,10a-hexahydro-3a,8,9-triaza-benzo[f]azulen-10-one (3.91 g, 13.8 mmol) in propionitrile (80 mL) and DMF (20 mL) was de-oxygenated with Ar for 25 min. The mixture was treated with tert-butyl acrylate (8.1 mL, 55 mmol) and (i-Pr)2EtN (5.1 mL, 29 mmol) and was de-oxygenated with Ar for 15 min. Pd(OAc)2 (0.31 g, 1.4 mmol) and P(o-tol)3 (0.84 mg, 2.8 mmol) were added simultaneously, and the mixture was de-oxygenated a third time for 10 min. The mixture was heated to reflux overnight then allowed to cool. The resulting precipitate was isolated by filtration, dissolved in CH2Cl2, filtered through Celite, and the solvent was removed in vacuo to give the title compound (2.53 g, 56%) as an off-white solid: MS (ESI) m/e 330 (M+H)+.

Workup

  1. waitwas de-oxygenated with Ar for 15 min
  2. customfor 10 min
  3. temperatureThe mixture was heated
  4. temperatureto reflux overnight
  5. temperatureto cool
  6. customThe resulting precipitate was isolated by filtration
  7. filtrationfiltered through Celite
  8. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-2c0354805c28490986fa3c452fc96e98
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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