Methyl Acrylate → HCID 86592040, compound

HRID 1785903Notes

Reaction equation

HRID 1785903 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([C:34](=[O:37])[CH2:35][CH3:36])[C@H:9]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([CH:19]=[CH:20][C:21]([OH:23])=[O:22])[CH:17]=3)[N:12]([C:24](=[O:32])[C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[C@@H:11]([CH3:33])[CH2:10]2)=[CH:4][CH:3]=1.Br[C:39]1C=C2C(=CC=1)N(C(=O)C1C=CC(F)=CC=1)[C@@H](C)C[C@H]2N(C1C=CC(Cl)=CC=1)C(=O)CC.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OC)(=O)C=C>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:39][O:22][C:21](=[O:23])[CH:20]=[CH:19][C:16]1[CH:17]=[C:18]2[C:13](=[CH:14][CH:15]=1)[N:12]([C:24](=[O:32])[C:25]1[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=1)[C@@H:11]([CH3:33])[CH2:10][C@H:9]2[N:8]([C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)[C:34](=[O:37])[CH2:35][CH3:36]

Participants

7

Reactant 4

HCID 7294Methyl AcrylateHCID 812191,3-Bis(diphenylphosphino)propaneHCID 86592037HCID 86592037, compound2×HCID 86592041HCID 86592041, compound

Product 1

HCID 86592040HCID 86592040, compoundYield 44%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

(±)-Cis-3-[4-[(4-chloro-phenyl)-propionyl-amino]-1-(4-fluoro-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-6-yl]-acrylic acid was made from (±)-cis-N-[6-bromo-1-(4-fluoro-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-N-(4-chloro-phenyl)-propionamide. To a solution of (±)-cis-N-[6-bromo-1-(4-fluoro-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-N-(4-chloro-phenyl)-propionamide (250 mg, 0.47 mmol), TEA (0.2 ml, 1.4 mmol), palladium acetate (11 mg, 0.047 mmol), 1,3-Bis(diphenylphosphino)propane (39 mg, 0.094 mmol), in 10 ml DMF was added 0.13 ml methyl acrylate (1.41 mmol). The resulting reaction mixture was heated to 80° C. overnight. The mixture was filtered through celite and the filtrate was concentrated under vacuum. The residue was purified by silica gel chromatography, eluting with ethyl acetate-hexane (2:3) to give (±)-cis-3-[4-[(4-chloro-phenyl)-propionyl-amino]-1-(4-fluoro-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-6-yl]-acrylic acid methyl ester (110 mg, 44%).

Workup

  1. customThe resulting reaction mixture
  2. filtrationThe mixture was filtered through celite
  3. concentrationthe filtrate was concentrated under vacuum
  4. customThe residue was purified by silica gel chromatography
  5. washeluting with ethyl acetate-hexane (2:3)

Sources & evidence

ORD record
ord-7f80f4ca960246edae8c256394ee132e
Source dataset
uspto-grants-2009_03
Patent number
US07504508B2

Reaction notes

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