1,2-Dichloroethane → 5-[1,3]Dioxolan-2-yl-4-methyl-thiophene-2-carboxylic acid hydrazide

HRID 1685695Notes

Reaction equation

HRID 1685695 reaction equation
[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[S:10][C:9]([C:11](O)=[O:12])=[CH:8][C:7]=1[CH3:14].C1C=CC2N(O)[N:22]=[N:21]C=2C=1.C(Cl)CCl.O.NN>C(O)(C)C.CN(C=O)C>[NH3:21].[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[S:10][C:9]([C:11]([NH:21][NH2:22])=[O:12])=[CH:8][C:7]=1[CH3:14]

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 24654Hydrazine hydrate (1:1)HCID 757711-HydroxybenzotriazoleHCID 672655315-[1,3]Dioxolan-2-yl-4-methyl-thiophene-2-carboxylic acid

Product 2

HCID 222AmmoniaHCID 672651755-[1,3]Dioxolan-2-yl-4-methyl-thiophene-2-carboxylic acid hydrazideYield 126.7%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of 5-formyl-4-methyl-thiophene-2-carboxylic acid (3.00 g, 17.6 mmol), ethylene glycol (3.28 g, 52.9 mmol) and p-toluene sulfonic acid hydrate (61 mg, 0.353 mmol) in toluene (80 mL) is refluxed for 3 h in a Dean-Stark apparatus. The clear solution is diluted with EA and washed twice with water. The washings are extracted back with EA. The combined organic extracts are dried over Na2SO4, filtered, concentrated and dried to give 5-[1,3]dioxolan-2-yl-4-methyl-thiophene-2-carboxylic acid (3.69 g) as a pale yellow resin, LC-MS: tR=0.46 min, [M+1]+=215.15. b) To a mixture of 5-[1,3]dioxolan-2-yl-4-methyl-thiophene-2-carboxylic acid (3.00 g, 14.0 mmol), HOBt (2.52 g, 16.8 mmol) and EDC (2.95 g, 15.4 mmol) in isopropanol (240 mL), hydrazine hydrate (1.50 g, 29.4 mmol) is added at 0° C. The suspension is stirred at 0° C., diluted with DMF and warmed to rt. Stirring is continued at rt for 2 h before the solvent is evaporated. The residue is dissolved in acetonitrile and separated by prep. HPLC (XBridge C18, 50×50 +100×50 mm, 10 μm, gradient of acetonitrile in water containing 0.5% of aq. ammonia) to give the title compound (2.43 g) as a colourless solid; LC-MS: tR=0.57 min, [M+1]+=228.96; 1H NMR (D6-DMSO): δ2.20 (s, 3H), 3.90-3.99 (m, 2H), 3.99-4.08 (m, 2H), 4.43 (s, 2H), 6.06 (s, 1H), 7.43 (s, 1H), 9.69 (s, 1H).

Workup

  1. additionis added at 0° C
  2. temperaturewarmed to rt
  3. stirringStirring
  4. customis evaporated
  5. dissolutionThe residue is dissolved in acetonitrile
  6. customseparated by prep

Sources & evidence

ORD record
ord-d3a8ce3f28be43d39d5bb0e45c529dda
Source dataset
uspto-grants-2012_04
Patent number
US08148410B2

Reaction notes

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