Iodine → Methyl 4-(1-hydroxyindan-1-yl)-crotonate

HRID 1377502Notes

Reaction equation

HRID 1377502 reaction equation
II.[C:3]1(=[O:12])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4]1.Br[CH2:14]/[CH:15]=[CH:16]/[C:17]([O:19][CH3:20])=[O:18].[Cl-].[NH4+]>O1CCCC1.[Zn]>[OH:12][C:3]1([CH2:14]/[CH:15]=[CH:16]/[C:17]([O:19][CH3:20])=[O:18])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4]1

Participants

7

Reactant 4

HCID 807IodineHCID 67351-IndanoneHCID 25517Ammonium ChlorideHCID 53691752-Butenoic acid, 4-bromo-, methyl ester

Product 1

HCID 22012252Methyl 4-(1-hydroxyindan-1-yl)-crotonateYield 44.4%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of activated zinc (80 g) in dry tetrahydrofuran (200 ml) was heated to reflux and a few crystals of iodine was added. A solution of 1-indanone (100 g) and methyl 4-bromo-crotonate (200 g) in 500 ml of dry tetrahydrofuran was added dropwise followed by reflux for 1 h. After cooling, ice and aq. ammonium chloride was added followed by extraction with dichloromethane. Removal of the solvent in vacuo gave a viscous oil which was purified on a silica gel column (eluent:dichloromethane/ether =1:1) giving methyl 4-(1-hydroxyindan-1-yl)-crotonate (78 g). A solution of the crotonate (20 g) was dissolved in 200 ml dry ether and added dropwise to a suspension of lithium aluminium hydride (10 g) in 150 ml of dry ether. After reflux for 1 h, the reaction mixture was hydrolyzed with water. Filtration, drying of the ether phase over magnesium sulfate, and removal of solvent in vacuo gave 4-(1-hydroxyindan-1-yl)-1-butanol (18 g) as an oil. The alcohol (16 g) was dissolved in methanol (250 ml) and concentrated hydrochloric acid (40 ml) was added. After stirring for 30 min at room temperature, the reaction mixture was concentrated in vacuo, water was added and the mixture extracted with ether. Drying of the ether phase over magnesium sulfate and removal of solvent in vacuo gave a viscous oil which was applied to a silica gel column (eluent:dichloromethane/ether=9:1) giving 4-((1H)inden-3-yl)-1-butanol (1.8 g). By the method described in EXAMPLE 2, the alcohol was converted to the corresponding methanesulfonate and the title compound, 27, was obtained using spiro[isobenzofuran-1(3H),4'-pi-peridine], mp: 79°-80° C.

Workup

  1. temperaturewas heated
  2. temperatureto reflux
  3. temperatureby reflux for 1 h
  4. temperatureAfter cooling
  5. extractionfollowed by extraction with dichloromethane
  6. customRemoval of the solvent in vacuo
  7. customgave a viscous oil which
  8. customwas purified on a silica gel column (eluent:dichloromethane/ether =1:1)

Sources & evidence

ORD record
ord-bac3289d58a747b385dc1d5132f3de78
Source dataset
uspto-grants-1997_09
Patent number
US05665725

Reaction notes

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