Trifluoroacetic acid → 5-Ethyl-2,3-dihydro-1,4-benzodioxine-6-carbohydrazide

HRID 229975Notes

Reaction equation

HRID 229975 reaction equation
C(OC([NH:8][NH:9][C:10]([C:12]1[CH:21]=[CH:20][C:15]2[O:16][CH2:17][CH2:18][O:19][C:14]=2[C:13]=1[CH2:22][CH3:23])=[O:11])=O)(C)(C)C.FC(F)(F)C(O)=O.[OH-].[Na+].O>O>[CH2:22]([C:13]1[C:14]2[O:19][CH2:18][CH2:17][O:16][C:15]=2[CH:20]=[CH:21][C:12]=1[C:10]([NH:9][NH2:8])=[O:11])[CH3:23]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 23719242Sodium hydroxide--water (1/1/1)HCID 59838592N'-(5-ethyl-2,3-dihydro-benzo[1,4]dioxine-6-carbonyl)-hydrazinecarboxylic acid tert-butyl ester

Product 1

HCID 450954525-Ethyl-2,3-dihydro-1,4-benzodioxine-6-carbohydrazideYield 129.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

5.15 g (16 mmol) of N′-(5-ethyl-2,3-dihydro-benzo[1,4]dioxine-6-carbonyl)-hydrazinecarboxylic acid tert-butyl ester were added to a 200 mL round bottom flask. About 20 mL of trifluoroacetic acid were added and the reaction mixture was stirred at room temperature for 24 hours. Then about 40 mL of water were added, followed by the slow addition of cold 10% NaOH/H2O, with stirring, until the acid was neutralized (pH ˜14). The reaction mixture was transferred to a separatory funnel and extracted with ethyl acetate by shaking gently (caution: gas evolution). The ethyl acetate extract was dried and evaporated to yield 5.51 g of a pale, viscous yellow semi-solid. The material was then placed in a 50° C. vacuum oven for about 1 hour to yield 4.62 g of 5-ethyl-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid hydrazide. The t-Boc cleavage is best accomplished with neat trifluoroacetic acid; use of adjunctive solvents always resulted in much lower yields. 1H NMR (CDCl3, 500 MHz) δ (ppm): 7.0 (br, 1H), 6.83 (m, 1H), 6.71 (m, 1H), 4.28 (br s, 4H), 2.76 (m, 2H), 1.6 (br, 2H), 1.17 (t, 3H).

Workup

  1. stirringwith stirring, until the acid
  2. customThe reaction mixture was transferred to a separatory funnel
  3. extractionextracted with ethyl acetate
  4. stirringby shaking gently (caution: gas evolution)
  5. extractionThe ethyl acetate extract
  6. customwas dried
  7. customevaporated
  8. customto yield 5.51 g of a pale, viscous yellow semi-solid
  9. customwas then placed in a 50° C.
  10. customfor about 1 hour

Sources & evidence

ORD record
ord-b3c9210f868249b2b4711c1f508b2bd7
Source dataset
uspto-grants-2009_07
Patent number
US07563928B2

Reaction notes

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