Hydrochloric Acid → 1-[(Pyridin-2-yl)methyl]-2,3-dihydro-1H-inden-1-ol

HRID 1983864Notes

Reaction equation

HRID 1983864 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH3:7].C([Li])CCC.[C:13]1(=[O:22])[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][CH2:14]1.Cl>O1CCCC1>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][C:13]1([OH:22])[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][CH2:14]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 67351-IndanoneHCID 79752-MethylpyridineHCID 178418339Butyllithium

Product 1

HCID 130480641-[(Pyridin-2-yl)methyl]-2,3-dihydro-1H-inden-1-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

A mixture of 29.5 ml (0.3 mol) of alpha-picoline with 140 ml of tetrahydrofuran was cooled to −20° C. and 187.5 ml of n-butyllithium (1.6M in hexane, 0.3 mol) were subsequently added while stirring. The mixture was allowed to warm to room temperature while stirring and a solution of 39.6 g (0.3 mol) of 1-indanone in 35 ml of tetrahydrofuran was then added over a period of 25 minutes while stirring. The mixture was then stirred for a further 1.5 hours and hydrolyzed with 600 ml of dilute hydrochloric acid, the organic phase was separated off and the aqueous phase was extracted once with diethyl ether. The aqueous phase was then neutralized with aqueous ammonia solution and extracted 3 times with 150 ml each time of chloroform. The organic phases were combined and the solvent was distilled off. The 1-(2-pyridinylmethyl)-1-indanol obtained in this way was dissolved using 500 ml of 10% strength by weight hydrochloric acid and heated for 3 hours on a waterbath. The reaction mixture was cooled, washed with ether and the aqueous phase was neutralized with aqueous ammonia solution. The neutralized aqueous phase was extracted 3 times with 150 ml each time of chloroform and the combined organic phases were dried over magnesium sulfate. After the magnesium sulfate had been filtered off, the solvent was distilled off to leave 52.7 g of a mixture of 2-(1H-inden-3-ylmethyl)pyridine and 2-[(E)-2,3-dihydro-1H-inden-1-ylidenemethyl]pyridine in a ratio of 10:9 in a total yield of 95%. NMR 1H (CDCl3): 8.61 (d, 1H); 7.61 (td, 1H); 7.55 (d, 1H); 7.51 (d, 1H); 7.36 (d, 1H); 7.32-7.22 (m, 3H); 7.16 (dd, 1H); 6.31 (m, 1H); 4.17 (br s, 2H); 3.43 (br s, 2H).

Workup

  1. temperatureto warm to room temperature
  2. stirringwhile stirring
  3. stirringwhile stirring
  4. customthe organic phase was separated off
  5. extractionthe aqueous phase was extracted once with diethyl ether
  6. extractionextracted 3 times with 150 ml each time of chloroform
  7. distillationthe solvent was distilled off

Sources & evidence

ORD record
ord-e9a57f3ab6544b7e93f43b33184d0726
Source dataset
uspto-grants-2009_06
Patent number
US07541473B2

Reaction notes

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