Methyl 1-benzothiophene-3-carboxylate → 1-Benzothiophen-3-ylmethanol

HRID 1377505Notes

Reaction equation

HRID 1377505 reaction equation
[S:1]1[CH:5]=[C:4]([C:6](OC)=[O:7])[C:3]2[CH:10]=[CH:11][CH:12]=[CH:13][C:2]1=2.[H-].[Al+3].[Li+].[H-].[H-].[H-]>CCOCC>[S:1]1[CH:5]=[C:4]([CH2:6][OH:7])[C:3]2[CH:10]=[CH:11][CH:12]=[CH:13][C:2]1=2

Participants

4

Reactant 2

HCID 12514024Methyl 1-benzothiophene-3-carboxylateHCID 21226445Aluminium lithium hydride

Product 1

HCID 27763421-Benzothiophen-3-ylmethanolYield 105.4%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

An ether solution (50 ml) of methyl benzo[b]thiophene-3-carboxylate (15 g) was added dropwise to a suspension of lithium aluminium hydride (3.5 g) in ether (100 ml) followed by reflux for 2 h. Usual work-up gave benzo[b]thiophen-3-yl methanol (13.5 g) as an oil. The oil was dissolved in tetrahydrofuran (50 ml) and added dropwise to a suspension of NaH (5 g of an 80% paraffinsuspension) in tetrahydrofuran (100 ml) followed by reflux for 1 h. Ethyl bromoacetate (35 g) in tetrahydrofuran (50 ml) was added at 60° C. followed by reflux for 1 h. Additional ethyl bromoacetate (20 g) was added followed by reflux for 7 h. The reaction was quenched with water and the volatiles removed in vacuo. The remaining oil was applied to a silica gel column (eluent:ethyl acetate/heptane 2:8) giving ethyl benzo[b]thiophen-3-ylmethyloxyacetate (5 g) as an oil. Reduction with lithium aluminium hydride as described above yielded 3.8 g of 2-(benzo[b]thiophen-3-ylmethyloxy)ethanol as an oil. The title compound 35a was obtained by the method described in EXAMPLE 2 using spiro[isobenzofuran-1(3H),4'-piperidine] and crystallized as the fumarate salt from an acetone/ethanol mixture by addition of fumaric acid. Yield: 0.55 g, mp: 149°-50° C.

Workup

  1. temperatureby reflux for 2 h

Sources & evidence

ORD record
ord-de17063987a64c01954d49bf373bb7bf
Source dataset
uspto-grants-1997_09
Patent number
US05665725

Reaction notes

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