Triethylamine → HCID 71150000, compound

HRID 1482743Notes

Reaction equation

HRID 1482743 reaction equation
[CH3:1][N:2]1[C@@H:19]2[CH2:20][C:7]3=[CH:8][CH:9]=[C:10](O)[C:11]4[O:12][C@H:13]5[C:14]([CH2:16][CH2:17][C@:18]2([OH:21])[C@:5]5([C:6]=43)[CH2:4][CH2:3]1)=[O:15].[O-]S(C(F)(F)F)(=O)=O.ON1[C:36](=[O:37])CCC1=O.C(N(CC)CC)C.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.Cl.[NH2:89][CH2:90][CH2:91][C:92]1[CH:97]=[CH:96][C:95]([C:98]2[CH:103]=[CH:102][NH:101][C:100](=[O:104])[CH:99]=2)=[CH:94][CH:93]=1>CS(C)=O.C(Cl)Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.CO>[OH:21][C@:18]12[C@H:19]3[CH2:20][C:7]4[C:6]5[C@@:5]1([CH2:4][CH2:3][N:2]3[CH3:1])[C@@H:13]([O:12][C:11]=5[C:10]([C:36]([NH:89][CH2:90][CH2:91][C:92]1[CH:93]=[CH:94][C:95]([C:98]3[CH:103]=[CH:102][NH:101][C:100](=[O:104])[CH:99]=3)=[CH:96][CH:97]=1)=[O:37])=[CH:9][CH:8]=4)[C:14](=[O:15])[CH2:16][CH2:17]2

Participants

11

Reactant 5

HCID 8471Triethylamine2×HCID 80170N-HydroxysuccinimideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)2×HCID 71150061HCID 71150061, compoundHCID 131736710HCID 131736710, compound

Product 1

HCID 71150000HCID 71150000, compoundYield 33%

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalyst2×HCID 679Dimethyl SulfoxideSolvent3×HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
70 °C

Procedure

Oxymorphone triflate (3.0 g, 7.0 mmol) was stirred in degassed DMSO (40 mL). N-hydroxysuccinimide (1.60 g, 13.9 mmol) was added followed by triethylamine (1.94 mL, 13.9 mmol), palladium acetate (156 mg, 0.7 mmol) and xantphos (402 mg, 0.7 mmol). The reaction mixture was stirred at 70° C. under an atmosphere of CO overnight. Further palladium acetate (1.04 g, 4.61 mmol) and xantphos (2.68 g, 4.63 mmol) were added and the reaction mixture heated 6 hours 70° C. under an atmosphere of CO. The mixture was allowed to return to room temperature before the addition of 4-(4-(2-aminoethyl)phenyl)pyridin-2(1H)-one hydrochloride (2.0 g, 8.0 mmol) and triethylamine (2 mL, 14.3 mmol). The reaction was stirred for 1 hour before removal of the DMSO under reduced pressure. The residue was subject to column chromatography (0 to 5% MeOH (NH3) in DCM). The isolated residue was found to still contain DMSO and was portioned between DCM (500 mL) and water (250 mL). The aqueous phase was extracted a further five times until the product was completely extracted. The organic phases were combined and the solvent removed under reduced pressure giving (4R,4aS,7aR,12bS)-4a-hydroxy-3-methyl-7-oxo-N-(4-(2-oxo-1,2-dihydropyridin-4-yl)phenethyl)-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-9-carboxamide (Compound-15; 1.2 g, 2.3 mmol, 33% yield).

Workup

  1. temperaturethe reaction mixture heated 6 hours 70° C. under an atmosphere of CO
  2. extractionThe aqueous phase was extracted a further five times until the product
  3. extractionwas completely extracted
  4. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-53ba0ee68250420aa7d85ed211017fca
Source dataset
uspto-grants-2016_08
Patent number
US09415045B2

Reaction notes

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