Acetic Acid → Ethyl 4-(5-isopropoxy-4-methoxy-2-nitrophenyl)-4-hydroxy-2-butynoate

HRID 1293555Notes

Reaction equation

HRID 1293555 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[C:13]([O:17][CH2:18][CH3:19])(=[O:16])[C:14]#[CH:15].[CH:20]([O:23][C:24]1[C:25]([O:35][CH3:36])=[CH:26][C:27]([N+:32]([O-:34])=[O:33])=[C:28]([CH:31]=1)[CH:29]=[O:30])([CH3:22])[CH3:21].C(O)(=O)C>O1CCCC1.O>[CH:20]([O:23][C:24]1[C:25]([O:35][CH3:36])=[CH:26][C:27]([N+:32]([O-:34])=[O:33])=[C:28]([CH:29]([OH:30])[C:15]#[C:14][C:13]([O:17][CH2:18][CH3:19])=[O:16])[CH:31]=1)([CH3:22])[CH3:21]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 7912DiisopropylamineHCID 12182Ethyl propiolateHCID 222225865-Isopropoxy-4-methoxy-2-nitrobenzaldehydeHCID 178418339Butyllithium

Product 1

HCID 22222636Ethyl 4-(5-isopropoxy-4-methoxy-2-nitrophenyl)-4-hydroxy-2-butynoateYield 114.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

1.5 N butyl lithium (22.6 ml, 33.8 mmol) was added to a solution of diisopropylamine (5.0 ml, 36.0 mmol) in tetrahydrofuran (75 ml) under an argon atmosphere at −78° C., and the mixture was stirred for one hr. Ethyl propiolate (2.9 ml, 28.2 mmol) and a solution of 5-isopropoxy-4-methoxy-2-nitrobenzaldehyde (4.5 g, 18.8 mmol) in tetrahydrofuran (50 ml) were then added thereto in that order, and the mixture was stirred at −78° C. for additional 1.5 hr. A solution of acetic acid (5.9 ml, 102 mmol) in tetrahydrofuran (20 ml) was added to the reaction solution. 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 hydrogencarbonate solution, and saturated brine solution. The organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give ethyl 4-(5-isopropoxy-4-methoxy-2-nitrophenyl)-4-hydroxy-2-butynoate (7.27 g). The resultant ethyl 4-(5-isopropoxy-4-methoxy-2-nitrophenyl)-4-hydroxy-2-butynoate was dissolved in toluene (60 ml). 4-Methoxybenzyl azide (9.2 g, 56.4 mmol) was added to the solution. The mixture was heated at 100° C. with stirring overnight. The reaction solution was cooled to room temperature. The solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:2) to give a 1:1 mixture (7.01 g, 75%) of ethyl 4-(1-hydroxy-(5-isopropoxy-4-methoxy-2-nitrophenyl)methyl)-1-(4-methoxybenzyl)-1H-1,2,3-triazole-5-carboxylate (a-1: low polar product (LP)) and ethyl 5-(1-hydroxy-(5-isopropoxy-4-methoxy-2-nitrophenyl)methyl)-1-(4-methoxybenzyl)-1H-1,2,3-triazole-4-carboxylate (a-2: high polar product (MP)).

Workup

  1. stirringin that order, and the mixture was stirred at −78° C. for additional 1.5 hr
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with dilute hydrochloric acid, water
  4. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-8ffff62e88f44b7c8af6bb0fb937d559
Source dataset
uspto-grants-2007_07
Patent number
US07238812B2

Reaction notes

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