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

HRID 2293331Notes

Reaction equation

HRID 2293331 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-8da6bdcaa6964a2ba769648260480419
Source dataset
uspto-grants-1997_11
Patent number
US05686442

Reaction notes

Loading…