Acetic Acid → HCID 18697784, compound

HRID 2289572Notes

Reaction equation

HRID 2289572 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]([O:17][CH2:18][CH3:19])(=[O:16])[C:14]#[CH:15].[CH2:20]1[O:30][C:29]2[C:22](=[CH:23][C:24]([N+:31]([O-:33])=[O:32])=[C:25]([CH:28]=2)[CH:26]=[O:27])[O:21]1.C(O)(=O)C>O1CCCC1.O>[OH:27][CH:26]([C:25]1[CH:28]=[C:29]2[O:30][CH2:20][O:21][C:22]2=[CH:23][C:24]=1[N+:31]([O-:33])=[O:32])[C:15]#[C:14][C:13]([O:17][CH2:18][CH3:19])=[O:16]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 7912DiisopropylamineHCID 12182Ethyl propiolateHCID 128406-Nitro-1,3-benzodioxole-5-carboxaldehydeHCID 178418339Butyllithium

Product 1

HCID 18697784HCID 18697784, compoundYield 119%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of diisopropylamine (6.8 ml, 49.0 mol) in tetrahydrofuran (80 ml) was added, at -78° C. under an argon atmosphere, a 1.5 N butyllithium (30.7 ml, 46.0 mmol). The mixture was stirred for one hr. Ethyl propiolate (3.9 ml, 38.4 mmol) and a solution of 4,5-methylenedioxy-2-nitrobenzaldehyde (5.0 g, 25.6 mmol) in tetrahydrofuran (50 ml) were added in that order to the reaction mixture, and the mixture was stirred at -78° C. for additional 1.5 hr. A solution of acetic acid (8.0 ml, 139 mmol) in tetrahydrofuran (20 ml) was then added to the reaction mixture, water was then added thereto, followed by extraction with ethyl acetate. The organic layer was washed with dilute hydrochloric acid, water, a saturated aqueous sodium bicarbonate solution, and saturated brine in that order. It was then dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give ethyl 4-hydroxy-4-(4,5-methylenedioxy-2-nitrophenyl)-2-butynoate as an oil (8.93 g). Ethyl 4-hydroxy-4-(4,5-methylenedioxy-2-nitrophenyl)-2-butynoate thus prepared was dissolved in toluene (75 ml), 4-methoxybenzylazide (14.9 g, 91.1 mmol) was added to the solution, and the mixture was stirred at 100° C. overnight. The reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:2) to give a 1:1 mixture of ethyl 4-(1-hydroxy-(4,5-methylenedioxy-2-nitrophenyl)methyl)-1-(4-methoxybenzyl)-1,2,3-triazole-5-carboxylate (a-1: low polar product (LP)) and ethyl 5-(1-hydroxy-(4,5-methylenedioxy-2-nitrophenyl)methyl)-1-(4-methoxybenzyl)-1,2,3-triazole-4-carboxylate (a-2: high polar product (MP)) (6.42 g, 55%).

Workup

  1. stirringthe mixture was stirred at -78° C. for additional 1.5 hr
  2. additionwas then added
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed with dilute hydrochloric acid, water
  5. dry with materialIt was then dried over anhydrous magnesium sulfate
  6. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-5dee3cbb2a3f4772a12b189d5c9ca5b6
Source dataset
uspto-grants-2000_07
Patent number
US06093714

Reaction notes

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