Acetic Acid → HCID 18937647, compound

HRID 2293336Notes

Reaction equation

HRID 2293336 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].[N+:20]([C:23]1[CH:30]=[C:29]([NH:31][C:32]([C:34]2[CH:39]=[CH:38][C:37]([CH3:40])=[CH:36][CH:35]=2)=[O:33])[CH:28]=[CH:27][C:24]=1[CH:25]=[O:26])([O-:22])=[O:21].C(O)(=O)C>O1CCCC1>[OH:26][CH:25]([C:24]1[CH:27]=[CH:28][C:29]([NH:31][C:32]([C:34]2[CH:39]=[CH:38][C:37]([CH3:40])=[CH:36][CH:35]=2)=[O:33])=[CH:30][C:23]=1[N+:20]([O-:22])=[O:21])[C:15]#[C:14][C:13]([O:17][CH2:18][CH3:19])=[O:16]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 7912DiisopropylamineHCID 12182Ethyl propiolateHCID 18937629HCID 18937629, compoundHCID 178418339Butyllithium

Product 1

HCID 18937647HCID 18937647, compoundYield 90.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of diisopropylamine (0.11 ml, 0.82 mmole) in tetrahydrofuran (2 ml) at -78° C. was added under the argon atmosphere 1.5N butyllithium (0.51 ml, 0.77 mmole), and the mixture was stirred for 30 minutes. Next, to this reaction mixture were added ethyl propiolate (93 μl, 0.92 mmole) followed by a solution of 2-nitro-4-(p-toluoylamino)-benzaldehyde (144.5 mg, 0.51 mmole), and the mixture was further stirred at -78° C. for 1 hour. After a solution of acetic acid (90 μl, 1.58 mmole) in tetrahydrofuran (1 ml) was added to the reaction mixture, it 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-(2-nitro-4-(p-toluoylamino)-phenyl)-2-butynoate as an oil (176 mg). The product thus obtained was dissolved in toluene (2 ml), 4-methoxybenzylazide (250 mg, 1.53 mmole), and the mixture was stirred with heating at 100° C. for 5 hours. The reaction mixture was cooled to room temperature, the resulting crystalline products were filtered to give the 1:1 mixture of ethyl 4-(hydroxy-(2-nitro-4-(p-toluoylamino)phenyl)methyl)-1-(4-methoxybenzyl)-1,2,3-triazole-5-carboxylate (a-1) and ethyl 5-(hydroxy-(2-nitro-4-(p-toluoylamino)phenyl)methyl)-1-(4-methoxybenzyl)-1,2,3-triazole-4-carboxylate (a-2) (103.4 mg, 37%).

Workup

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

Sources & evidence

ORD record
ord-617bfeb16e38438cbd21349b7041b7d0
Source dataset
uspto-grants-1997_11
Patent number
US05686442

Reaction notes

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