3-Bromo-1-propanol → HCID 19698759, compound

HRID 2288162Notes

Reaction equation

HRID 2288162 reaction equation
[OH:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[CH:10]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([O:19][CH2:20][CH2:21][CH3:22])[CH:17]=2)[CH:12]([C:23]2[CH:28]=[CH:27][C:26]3[O:29][CH2:30][O:31][C:25]=3[CH:24]=2)[CH:11]1[C:32]([O:34][CH3:35])=[O:33].[H-].[Na+].Br[CH2:39][CH2:40][CH2:41][OH:42]>CN(C=O)C>[OH:42][CH2:41][CH2:40][CH2:39][O:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[CH:10]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([O:19][CH2:20][CH2:21][CH3:22])[CH:17]=2)[CH:12]([C:23]2[CH:28]=[CH:27][C:26]3[O:29][CH2:30][O:31][C:25]=3[CH:24]=2)[CH:11]1[C:32]([O:34][CH3:35])=[O:33]

Participants

5

Reactant 3

HCID 123083-Bromo-1-propanolHCID 24758Sodium hydrideHCID 10205815HCID 10205815, compound

Product 1

HCID 19698759HCID 19698759, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Methyl (1RS,2RS,3RS)-3-(2-Hydroxy-4-methoxy-phenyl)-1-(3,4-methylenedioxyphenyl)-5-(prop-1-yloxy)-indane-2-carboxylate (0.14 g, 0.29 mmol) in dry DMF (1 ml) was added to NaH (9 mg, 0.38 mmol) in a small volume of dry DMF. The mixture was stirred at ambient temperature for 20 min. then 3-bromopropan-1-ol (37 μl, 0.41 mmol) was added. After stirring for 1 h. the product was partitioned between 3 M aqueous HCl and ethyl acetate. The organic layer was washed with water then brine, then dried (MgSO4 anhyd.) filtered and evaporated to give an oil. The product was purified by column chromatography to provide methyl (1RS,2RS,3RS)-3-[2-(3-Hydroxyprop-1-yloxy)-4-methoxyphenyl]-1-(3,4-methylenedioxyphenyl)-5-(prop-1-yloxy)indane-2-carboxylate (0.1 g, 65%)(1H-NMR indicated some epimerization had occurred at C-2). This material was used without further purification. Methyl (1RS,2RS,3RS)-3-[2-(3-Hydroxyprop-1-yloxy)-4-methoxyphenyl]-1-(3,4-methylenedioxyphenyl)-5-(prop-1-yloxy)-indane-2-carboxylate (0.04 g, 0.075 mmol) was dissolved in methanol (2 ml) and aqueous potassium hydroxide added (2 M, 0.22 ml, 0.44 mmol). The mixture was stirred under reflux overnight then cooled, diluted with water, acidified with 3 M aqueous hydrochloric acid and extracted with ethyl acetate. The organic extract was washed with water and brine, dried (MgSO4 anhydrous), filtered and evaporated to give an oil. The product was purified by chromatography on silica-gel (eluant: ethyl acetate/hexane/3% acetic acid) to give 12 mg of free acid which was converted to its dicyclohexylamine salt. m.p. 110-112° C.

Workup

  1. stirringAfter stirring for 1 h. the product
  2. customwas partitioned between 3 M aqueous HCl and ethyl acetate
  3. washThe organic layer was washed with water
  4. dry with materialbrine, then dried (MgSO4 anhyd.)
  5. filtrationfiltered
  6. customevaporated
  7. customto give an oil
  8. customThe product was purified by column chromatography

Sources & evidence

ORD record
ord-813e3e81ff514458a79f2aabeb3d0f93
Source dataset
uspto-grants-2000_07
Patent number
US06087389

Reaction notes

Loading…