Acetic Acid → Ethyl 4-hydroxy-4-(4,5-dimethoxy-2-nitrophenyl)-2-butynoate

HRID 2293324Notes

Reaction equation

HRID 2293324 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].[CH3:20][O:21][C:22]1[C:29]([O:30][CH3:31])=[CH:28][C:25]([CH:26]=[O:27])=[C:24]([N+:32]([O-:34])=[O:33])[CH:23]=1.C(O)(=O)C>O1CCCC1.O>[OH:27][CH:26]([C:25]1[CH:28]=[C:29]([O:30][CH3:31])[C:22]([O:21][CH3:20])=[CH:23][C:24]=1[N+:32]([O-:34])=[O:33])[C:15]#[C:14][C:13]([O:17][CH2:18][CH3:19])=[O:16]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 7912DiisopropylamineHCID 12182Ethyl propiolateHCID 885056-NitroveratraldehydeHCID 178418339Butyllithium

Product 1

HCID 15672998Ethyl 4-hydroxy-4-(4,5-dimethoxy-2-nitrophenyl)-2-butynoateYield 117.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

1.5N butyllithium (26.8 ml, 40.2 mmole) was added under the argon atmosphere to a solution of diisopropylamine (6.0 ml, 42.8 mmole) in tetrahydrofuran (75 ml) at -78° C., and the mixture was stirred for 1 hour. Next, ethyl propiolate (3.4 ml, 33.5 mmole) and a solution of 4,5-dimethoxy-2-nitrobenzaldehyde (5.0 g, 23.7 mmole) in tetrahydrofuran (50 ml) were added in this sequence, and the reaction mixture was stirred at -78° C. for further 1.5 hours. After a solution of acetic acid (7.0 ml, 122 mmole) in tetrahydrofuran (20 ml) followed by water were added, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with dilute hydrochloric acid, water, a saturated aqueous sodium hydrogen carbonate solution and a saturated aqueous saline in this sequence. After the organic layer was dried over anhydrous magnesium sulfate, the solvent was removed under reduced pressure to give ethyl 4-hydroxy-4(4,5-dimethoxy-2-nitrophenyl)-2-butynoate as an oil (8.59 g). Ethyl 4-hydroxy-4(4,5-dimethoxy-2-nitrophenyl)-2-butynoate thus obtained was dissolved in toluene (80 ml), 4-methoxybenzylazide (11.6 g, 71.1 mmole) was added, and the mixture was stirred under heating at 100° C. overnight. After the reaction mixture was cooled to room temperature, it was purified by silica gel column chromatography (hexane:ethyl acetate=2:1).

Workup

  1. stirringthe reaction mixture was stirred at -78° C. for further 1.5 hours
  2. additionwere added
  3. extractionthe reaction mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with dilute hydrochloric acid, water
  5. dry with materialAfter the organic layer was dried over anhydrous magnesium sulfate
  6. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-232a7c7db57a4ef093221266da1c943a
Source dataset
uspto-grants-1997_11
Patent number
US05686442

Reaction notes

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