Acetic Acid → Ethyl 4-hydroxy-4-(4-methyl-2-nitrophenyl)-2-butynoate

HRID 357656Notes

Reaction equation

HRID 357656 reaction equation
[C:1]([O:5][CH2:6][CH3:7])(=[O:4])[C:2]#[CH:3].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:18][C:19]1[CH:26]=[CH:25][C:22]([CH:23]=[O:24])=[C:21]([N+:27]([O-:29])=[O:28])[CH:20]=1.C(=O)([O-])O.[Na+].C(O)(=O)C>O1CCCC1.O>[OH:24][CH:23]([C:22]1[CH:25]=[CH:26][C:19]([CH3:18])=[CH:20][C:21]=1[N+:27]([O-:29])=[O:28])[C:3]#[C:2][C:1]([O:5][CH2:6][CH3:7])=[O:4]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 12182Ethyl propiolateHCID 516892Sodium BicarbonateHCID 5904464-Methyl-2-nitrobenzaldehydeHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 18937622Ethyl 4-hydroxy-4-(4-methyl-2-nitrophenyl)-2-butynoateYield 102.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent4×

Procedure

(a-1) To a solution of ethyl propiolate (6.6 ml, 65 mmole) in tetrahydrofuran (70 ml) was added at -65° C. under the argon atmosphere a solution of 1.0M lithium bistrimethylsilylamide in tetrahydrofuran (65 ml, 65 mmole), and the mixture was stirred for 20 minutes. A solution of 4-methyl-2-nitrobenzaldehyde (8.3 g, 50 mmole) in tetrahydrofuran (30 ml) was added, and the reaction mixture was further stirred at 65° C. for 3 hours. To the reaction mixture was added a saturated aqueous sodium hydrogen carbonate solution (80 ml) or a solution of acetic acid (13.0 ml, 220 mmole) in tetrahydrofuran (20 ml), followed by water, and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with dilute hydrochloric acid, a saturated aqueous sodium hydrogen carbonate solution and a saturated aqueous saline in this sequence, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to give ethyl 4-hydroxy-4-(4-methyl-2-nitrophenyl)-2-butynoate as an oil (13.5 g).

Workup

  1. stirringthe reaction mixture was further stirred at 65° C. for 3 hours
  2. extractionthe aqueous layer was extracted with ethyl acetate
  3. washThe organic layer was washed with dilute hydrochloric acid
  4. dry with materiala saturated aqueous sodium hydrogen carbonate solution and a saturated aqueous saline in this sequence, dried over anhydrous sodium sulfate
  5. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-d5f3a20c51cb46bf98ec3a8e22d4267a
Source dataset
uspto-grants-1998_11
Patent number
US05840895

Reaction notes

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