Hydrochloric Acid → 3-Benzyl-9-methoxy-5-methoxymethyl-1,2,3,4,5,6,7,7a-octahydro4a,7-ethanobenzofuro[3,2-e]isoquinoline

HRID 35527Notes

Reaction equation

HRID 35527 reaction equation
[H-].[K+].[CH2:3]([N:10]1[CH2:19][CH2:18][C:17]23[C:20]4[CH:26]=[CH:25][CH:24]=[C:23]([O:27][CH3:28])[C:21]=4[O:22][CH:16]2[CH:15]2[CH2:29][CH2:30][C:12]3([CH:13]([CH2:31][OH:32])[CH2:14]2)[CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH3:33]I.Cl>O1CCCC1.CCCCCC>[CH2:3]([N:10]1[CH2:19][CH2:18][C:17]23[C:20]4[CH:26]=[CH:25][CH:24]=[C:23]([O:27][CH3:28])[C:21]=4[O:22][CH:16]2[CH:15]2[CH2:29][CH2:30][C:12]3([CH:13]([CH2:31][O:32][CH3:33])[CH2:14]2)[CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 82127Potassium hydrideHCID 212944713-Benzyl-5-hydroxymethyl-9-methoxy-1,2,3,4,5,6,7,7a-octahydro-4a,7-ethanobenzofuro[3,2-e]isoquinoline

Product 1

HCID 212944683-Benzyl-9-methoxy-5-methoxymethyl-1,2,3,4,5,6,7,7a-octahydro4a,7-ethanobenzofuro[3,2-e]isoquinolineYield 102.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

To a suspension of 12.0 g of 35% potassium hydride in oil, prewashed with hexane, in 100 mL of tetrahydrofuran was added a solution of 9.91 g of 3-benzyl-5-hydroxymethyl-9-methoxy-1,2,3,4,5,6,7,7a-octahydro-4a,7-ethanobenzofuro[3,2-e]isoquinoline (E. Ciganek and B. K. Wong, coassigned pending application, U.S. Ser. No. 774,025) in 50 mL of tetrahydrofuran and the mixture was heated under reflux for 4 hours. Methyl iodide (5.2 g dissolved in 10 mL of tetrahydrofuran) was added to the cooled mixture which was then stirred at room temperature for 18 hours. Addition of 5% hydrochloride acid followed by aqueous ammonium hydroxide solution and extraction with methylene chloride gave 10.47 g of 3-benzyl-9-methoxy-5-methoxymethyl-1,2,3,4,5,6,7,7a-octahydro4a,7-ethanobenzofuro[3,2-e]isoquinoline. NMR spectrum (δ in CDCl3): 7.5-7.2 (m, 7H); 6.8 (m, 2H); 4.4 (s, 1H); 3.9 (s, 3H), 3.7 (d, J=12 Hz, 1H); 3.5 (d, J=12 H, 1H) and 3.2 (s, 3H), among others.

Workup

  1. temperatureunder reflux for 4 hours
  2. extractionfollowed by aqueous ammonium hydroxide solution and extraction with methylene chloride

Sources & evidence

ORD record
ord-31b5308afbd6494484198368daa73c61
Source dataset
uspto-grants-1988_08
Patent number
US04767764

Reaction notes

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