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

HRID 1774041Notes

Reaction equation

HRID 1774041 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 sinking 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. extractionThe ethyl acetate extract
  5. customwas dried
  6. customevaporated
  7. customto yield 5.51 g of a pale, viscous yellow semi-solid
  8. customwas then placed in a 50° C.
  9. customfor about 1 hour

Sources & evidence

ORD record
ord-318fe8b0043f4bbca33fb9426db50359
Source dataset
uspto-grants-2016_02
Patent number
US09255273B2

Reaction notes

Loading…