Methanol → Trans-1,2,3,5,6,10b-Hexahydro-6-[4'-(3-hydroxy-1-propenyl)phenyl]pyrrolo[2,1-a]isoquinoline

HRID 1275487Notes

Reaction equation

HRID 1275487 reaction equation
C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Br[C:21]1[CH:26]=[CH:25][C:24]([C@H:27]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[C@H:30]3[CH2:37][CH2:38][CH2:39][N:29]3[CH2:28]2)=[CH:23][CH:22]=1.[CH2:40]([OH:43])[C:41]#[CH:42].CO>C(N(CC)CC)C.C(Cl)Cl.CC([O-])=O.CC([O-])=O.[Pd+2].[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:43][CH2:40][CH:41]=[CH:42][C:21]1[CH:26]=[CH:25][C:24]([C@H:27]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[C@H:30]3[CH2:37][CH2:38][CH2:39][N:29]3[CH2:28]2)=[CH:23][CH:22]=1

Participants

10

Reactant 4

HCID 887MethanolHCID 7859Propargyl alcoholHCID 11776TriphenylphosphineHCID 10830104trans-1,2,3,5,6,10b-Hexahydro-6-(4'-bromophenyl)pyrrolo[2,1-a]isoquinoline

Product 1

HCID 54066242Trans-1,2,3,5,6,10b-Hexahydro-6-[4'-(3-hydroxy-1-propenyl)phenyl]pyrrolo[2,1-a]isoquinoline

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 167845palladium(II) acetateCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent3×

Procedure

To a stirred solution of Pd(OAc)2 (17 mg, 0.07 mmol), Ph3P (35 mg, 0.14 mmol), CuI (15 mg), Pd(Ph3P)4 (10 mg) in 5 mL of triethylamine was added a solution of trans-1,2,3,5,6,10b-hexahydro-6-(4'-bromophenyl)pyrrolo[2,1-a]isoquinoline (440 mg, 1.34 mmol) in 15 mL of triethylamine at room temperature followed by addition of propargyl alcohol (208 mg, 3.67 mmol). The reaction mixture was teated at reflux overnight, cooled to room temperature, quenched with sat'd NaHCO3 solution (20 mL), extracted with methylene chloride (3×20 mL). The combined methylene chloride extract was dried over anhydrous MgSO4, filtered and concentrated to afford a crude product mixture. Flash chromatography with 3.5% MeOH, 0.07% Et3N in methylene chloride gave starting material 280 mg (64% recovery) and 58 mg of thick orange oil (58% conversion yield). 1H NMR (CDCl3) δ 1.73-2.05 (m, 3H, C2H2 & C1H), 2.30-2.2.44 (m, 1H, C1H), 2.579 (dt, 1H, J=9.0, 8.7 Hz, C3H), 2.869 (dd, 1H, J=5.1, 11.1 Hz, C5H), 2.90-3.03 (m, 2H, C3H & C5H), 3.480 (dd, 1H, J=7.2, 9.0 Hz, C10bH), 4.125 (t, 1H, J=4.8 Hz, C6H), 6.865 (d, 1H, J=7.5 Hz, aryl), 6.995 (d, 2H, J=8.1 Hz, C6 phenyl aryl), 7.04-7.20 (m, 3H, aryl), 7.575 (d, 2H, J=8.1 Hz, C6 phenyl aryl); 13C NMR (CDCl3) δ 22.17 (C2), 30.31 (C1), 45.48 (C3), 54.13 (C10b), 55.95 (C6), 63.67 (C5), 91.60 (4'C), 125.73 (aromatic), 126.30, 129.30, 130.97, 137.23.

Workup

  1. temperatureat reflux overnight
  2. customquenched with sat'd NaHCO3 solution (20 mL)
  3. extractionextracted with methylene chloride (3×20 mL)
  4. extractionThe combined methylene chloride extract
  5. dry with materialwas dried over anhydrous MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford a crude product mixture

Sources & evidence

ORD record
ord-04de8ffa5157423a8f9bda475b5d1b8a
Source dataset
uspto-grants-2000_12
Patent number
US06162417

Reaction notes

Loading…