Methyl vinyl ketone → HCID 86739698, compound

HRID 1632766Notes

Reaction equation

HRID 1632766 reaction equation
[CH2:1]([N:8]1[CH2:17][CH2:16][C:15]23[C:18]4[CH:24]=[CH:23][CH:22]=[C:21]([O:25][CH3:26])[C:19]=4[O:20][C:14]2=[CH:13][CH:12]=[CH:11][C:10]3=[CH:9]1)[C:2]1[CH:7]=[CH:6]C=CC=1.[C:27]([O:31]C)(=[O:30])[CH:28]=[CH2:29].C1C2NC3C(=CC=CC=3)SC=2C=CC=1.C(C(C)=[O:50])=C.[OH-].[Na+]>[Pd].O1CCCC1>[C:27]([CH:28]1[C:10]23[CH2:11][CH2:12][CH:13]([CH:14]4[O:20][C:19]5[C:21]([O:25][CH3:26])=[CH:22][CH:23]=[CH:24][C:18]=5[C:15]42[CH2:16][CH2:17][N:8]([CH2:1][CH:2]2[CH2:7][CH2:6]2)[C:9]3=[O:50])[CH2:29]1)([OH:31])=[O:30]

Participants

8

Reactant 5

HCID 6570Methyl vinyl ketoneHCID 7108PhenothiazineHCID 7294Methyl AcrylateHCID 14798Sodium HydroxideHCID 54222893HCID 54222893, compound

Product 1

HCID 86739698HCID 86739698, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 1.50 g of 3-cyclopropylmethyl-9-methoxy-2,3-dihydro-1H-benzofuro[3,2-e]isoquinolin-4-(7aH)-one (III; ##STR26## R2 =OMe), 10 mL of methyl acrylate and 0.01 g of phenothiazine, contained in an evacuated and sealed Carius tube, was heated to 130° for 6 hours. Removal of the excess methyl acrylate gave 2.17 g of 3:1 mixture of two isomers of 3-cyclopropylmethyl-9-methoxy-5-methoxycarbonyl-1,2,5,6,7,7a-hexahydro-4a,7-ethenobenzofuro[3,2-e]isoquinolin-4(3H)-one (IV; ##STR27## R2 =OMe, R3 =CO2CH3). 220 MHz NMR spectroscopy showed that the major isomer had the same stereochemistry as the corresponding methyl vinyl ketone adduct (Example 7). The mixture was subjected to catalytic hydrogenation (30 mL tetrahydrofuran, 1.04 g of 10% Pd/C, room temperature, overnight) and the product so obtained was hydrolyzed by heating under reflux with aqueous methanolic sodium hydroxide followed by acidification to give 1.52 g of 5-carboxy-3-cyclopropylmethyl-9-methoxy-1,2,5,6,7,7a-hexahydro-4a,7-ethanobenzofuro[3,2-e]isoquinolin-4(3H)-one (V; ##STR28## R2 =OMe, R3 =CO2H) as a mixture of two isomers. Reduction with borane methyl sulfide and demethylation as described in Examples 1 and 2 gave 1.72 g of crude product which on crystallization from dimethylformamide gave 0.62 g of a single isomer of 3-cyclopropylmethyl-5-hydroxymethyl-1,2,3,4,5,6,7,7a-octahydro-4a,7-ethanobenzofuro[3,2-e]isoquinolin-9-ol, m.p. 187°-190°.

Workup

  1. customan evacuated
  2. customsealed Carius tube
  3. temperaturewas heated to 130° for 6 hours
  4. customRemoval of the excess methyl acrylate
  5. customgave
  6. customthe product so obtained
  7. temperatureby heating

Sources & evidence

ORD record
ord-e058d7763cf8430a93e6f5284e296c7a
Source dataset
uspto-grants-1984_10
Patent number
US04477456

Reaction notes

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