Triethylamine → HCID 117857709, compound

HRID 1483154Notes

Reaction equation

HRID 1483154 reaction equation
FC(F)(F)S(OC1C2[O:13][C@H:14]3[C:23](=[O:24])[CH2:22][CH2:21][C@:20]4([OH:25])[C@@:15]53[CH2:16][CH2:17][N:18]([CH2:27][CH:28]3[CH2:31][CH2:30][CH2:29]3)[C@@H:19]4[CH2:26][C:10](C=25)=[CH:9][CH:8]=1)(=O)=O.O[N:35]1[C:39](=[O:40])[CH2:38][CH2:37][C:36]1=O.C(N(CC)CC)C.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.[C]=O.[CH3:93][O:94][C:95]1[CH:102]=[C:101]([O:103][CH3:104])[CH:100]=[CH:99][C:96]=1[CH2:97]N>CS(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:28]1([CH2:27][N:18]2[CH2:17][CH2:16][C@@:15]34[C:36]5[C:10]6[CH2:26][C@@H:19]2[C@:20]3([OH:25])[CH2:21][CH2:22][C:23](=[O:24])[C@@H:14]4[O:13][C:37]=5[C:38]([C:39]([NH:35][CH2:97][C:96]2[CH:99]=[CH:100][C:101]([O:103][CH3:104])=[CH:102][C:95]=2[O:94][CH3:93])=[O:40])=[CH:8][CH:9]=6)[CH2:29][CH2:30][CH2:31]1

Participants

9

Reactant 6

HCID 8471TriethylamineHCID 80170N-HydroxysuccinimideHCID 5972502,4-DimethoxybenzylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 117857399HCID 117857399, compoundHCID 178418416HCID 178418416, compound

Product 1

HCID 117857709HCID 117857709, compoundYield 92.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of (4R,4aS,7aR,12bS)-3-(cyclobutylmethyl)-4a-hydroxy-7-oxo-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-9-yl trifluoromethanesulfonate (14.3 g, 29.3 mmol) in degassed dimethyl sulfoxide (185 mL), was added N-hydroxysuccinimide (6.8 g, 58.7 mmol), palladium acetate (0.66 g, 2.93 mmol), triethylamine (8.2 mL, 58.7 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (1.7 g, 2.93 mmol). The reaction mixture was heated with carbon monoxide (1 atm) at 75° C. overnight. The reaction mixture was cooled to ambient temperature and 2,4-dimethoxybenzylamine (4.9 g, 29.3 mmol) added. The mixture was stirred for 1 hour before partitioning between water (2 L) and ethyl acetate (1 L). The aqueous phase was extracted twice more with ethyl acetate. The combined organic phase was dried (MgSO4), filtered, and the solvent removed under reduced pressure. The crude material was purified by silica chromatography (3% methanol in dichloromethane) to give (4R,4aS,7aR,12bS)-3-(cyclobutylmethyl)-N-(2,4-dimethoxybenzyl)-4a-hydroxy-7-oxo-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-9-carboxamide (14.4 g, 55% yield); LC/MS (M+H)+=533.3.

Workup

  1. custombefore partitioning between water (2 L) and ethyl acetate (1 L)
  2. extractionThe aqueous phase was extracted twice more with ethyl acetate
  3. dry with materialThe combined organic phase was dried (MgSO4)
  4. filtrationfiltered
  5. customthe solvent removed under reduced pressure
  6. customThe crude material was purified by silica chromatography (3% methanol in dichloromethane)

Sources & evidence

ORD record
ord-fbe8f2762ea24e40916d276ef65b90d2
Source dataset
uspto-grants-2016_08
Patent number
US09416137B2

Reaction notes

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