Acetic Acid → HCID 18697797, compound

HRID 2289571Notes

Reaction equation

HRID 2289571 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].[CH:20]([O:23][C:24]1[C:31]([O:32][CH:33]([CH3:35])[CH3:34])=[CH:30][C:27]([CH:28]=[O:29])=[C:26]([N+:36]([O-:38])=[O:37])[CH:25]=1)([CH3:22])[CH3:21].C(O)(=O)C>O1CCCC1.O>[CH:20]([O:23][C:24]1[C:31]([O:32][CH:33]([CH3:35])[CH3:34])=[CH:30][C:27]([CH:28]([OH:29])[C:15]#[C:14][C:13]([O:17][CH2:18][CH3:19])=[O:16])=[C:26]([N+:36]([O-:38])=[O:37])[CH:25]=1)([CH3:21])[CH3:22]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 7912DiisopropylamineHCID 12182Ethyl propiolateHCID 18697803HCID 18697803, compoundHCID 178418339Butyllithium

Product 1

HCID 18697797HCID 18697797, compoundYield 114.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of diisopropylamine (5.0 ml, 36.0 mmol) in tetrahydrofuran (75 ml) was added, at -78° C. under an argon atmosphere, a 1.5 N butyllithium (22.6 ml, 33.8 mmol). The mixture was stirred for one hr. Ethyl propiolate (2.9 ml, 28.2 mmol) and a solution of 4,5-diisopropoxy-2-nitrobenzaldehyde (5.0 g, 18.7 mmol) in tetrahydrofuran (50 ml) were added 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 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. The resultant mixture was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1) to give ethyl 4-(4,5-diisopropoxy-2-nitrophenyl)-4-hydroxy-2-butynoate (7.80 g). Ethyl 4-(4,5-diisopropoxy-2-nitrophenyl)-4-hydroxy-2-butynoate thus obtained was dissolved in toluene (60 ml), 4-methoxybenzylazide (10.5 g, 64.4 mmol) was added thereof, and the mixture was stirred at 100° C. for 9 hr. 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-diisopropoxy-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-diisopropoxy-2-nitrophenyl)methyl)-1-(4-methoxybenzyl)-1,2,3-triazole-4-carboxylate (a-2: high polar product (MP)) (5.34 g, 54%).

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
  7. customThe resultant mixture was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-1d016add25344152be6c629dda2f585c
Source dataset
uspto-grants-2000_07
Patent number
US06093714

Reaction notes

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