Potassium hydride → 5-cinnamyloxymethyl-3-cyclopropylmethyl-9-methoxy-1,2,5,6,7,7a-hexahydro-4a,7-ethanobenzofuro[3,2-e]isoquinolin-4(3H)-one

HRID 35528

Reaction equation

HRID 35528 reaction equation
[H-].[K+].[CH:3]1([CH2:6][N:7]2[CH2:16][CH2:15][C:14]34[C:17]5[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[C:18]=5[O:19][CH:13]3[CH:12]3[CH2:26][CH2:27][C:9]4([CH:10]([CH2:28][OH:29])[CH2:11]3)[C:8]2=[O:30])[CH2:5][CH2:4]1.C1(CN2[CH2:44][CH2:43][C:42]34C5C=CC=C(OC)C=5OC3[CH:40]3[CH2:54][CH2:55][C:37]4([CH:38](C(OC)=O)[CH2:39]3)C2=O)CC1.C(Br)C=CC1C=CC=CC=1>O1CCCC1.C(Cl)Cl.O.CCCCCC>[CH2:44]([O:29][CH2:28][CH:10]1[C:9]23[CH2:27][CH2:26][CH:12]([CH:13]4[O:19][C:18]5[C:20]([O:24][CH3:25])=[CH:21][CH:22]=[CH:23][C:17]=5[C:14]42[CH2:15][CH2:16][N:7]([CH2:6][CH:3]2[CH2:5][CH2:4]2)[C:8]3=[O:30])[CH2:11]1)[CH:43]=[CH:42][C:37]1[CH:55]=[CH:54][CH:40]=[CH:39][CH:38]=1

Participants

9

Reactant 4

HCID 82127Potassium hydrideHCID 98116BromomethylstyreneHCID 212944573-cyclopropylmethyl-9-methoxy-5-methoxycarbonyl-1,2,5,6,7,7a-hexahydro-4a,7-ethanobenzofuro[3,2-e]isoquinolin-4(3H)-oneHCID 212944613-cyclopropylmethyl-5-hydroxymethyl-9-methoxy-1,2,5,6,7,7a-hexahydro-4a,7-ethanobenzofuro[3,2-e]isoquinolin-4(3H)-one

Product 1

HCID 704165665-cinnamyloxymethyl-3-cyclopropylmethyl-9-methoxy-1,2,5,6,7,7a-hexahydro-4a,7-ethanobenzofuro[3,2-e]isoquinolin-4(3H)-one

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

To a solution of 2.06 g of 35% potassium hydride in oil, prewashed with hexane, in 15 mL of tetrahydrofuran was added 0.70 g of 3-cyclopropylmethyl-5-hydroxymethyl-9-methoxy-1,2,5,6,7,7a-hexahydro-4a,7-ethanobenzofuro[3,2-e]isoquinolin-4(3H)-one (synthesized by following the procedures of Example 1, Method A, using 3-cyclopropylmethyl-9-methoxy-5-methoxycarbonyl-1,2,5,6,7,7a-hexahydro-4a,7-ethanobenzofuro[3,2-e]isoquinolin-4(3H)-one, U.S. Pat. No. 4,477,456, as the starting material) and the mixture was heated under reflux for 30 min. Cinnamyl bromide (2 mL) was added to the cooled mixture which was then heated under reflux for 20 minutes. Water and methylene chloride were added, and the aqueous layer was extracted with methylene chloride. Removal of the solvent from the dried organic phases gave 0.84 of 5-cinnamyloxymethyl-3-cyclopropylmethyl-9-methoxy-1,2,5,6,7,7a-hexahydro-4a,7-ethanobenzofuro[3,2-e]isoquinolin-4(3H)-one. NMR spectrum (δ in CDCl3): 7.1-7.4 (m, 5H); 6.8 (m, 2H); 6.7 (m, 1H); 6.6 (d, J=15 Hz, 1H); 6.3 (d/t, J=15/7 Hz, 1H), 4.4 (s, 1H); 5.8 (m, 2H); 3.9 (s, 3H); 0.5 (m, 2H); and 0.2 (m, 2H), among others.

Workup

  1. customsynthesized
  2. temperature4,477,456, as the starting material) and the mixture was heated
  3. temperatureunder reflux for 30 min
  4. temperaturewas then heated
  5. temperatureunder reflux for 20 minutes
  6. extractionthe aqueous layer was extracted with methylene chloride
  7. customRemoval of the solvent from the dried organic phases

Sources & evidence

ORD record
ord-7ed96d5c211b4ecca6f4426ef547f4ce
Source dataset
uspto-grants-1988_08
Patent number
US04767764

Linked notes

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