2,2-Dimethyl-3-pentanone → 5-Methyl-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid n'-(1-ethyl-2,2-dimethyl-propyl)-hydrazide

HRID 2199435Notes

Reaction equation

HRID 2199435 reaction equation
CC1OC2C=CC(C(NN)=O)=CC=2OC1.CC(C)(C(=O)CC)C.[CH2:24]([C:26](=[N:31][NH:32][C:33]([C:35]1[CH:44]=[CH:43][C:38]2[O:39][CH2:40][CH2:41][O:42][C:37]=2[C:36]=1[CH3:45])=[O:34])[C:27]([CH3:30])([CH3:29])[CH3:28])[CH3:25].C([BH3-])#N.[Na+]>C(O)(=O)C.C(O)C>[CH2:24]([CH:26]([NH:31][NH:32][C:33]([C:35]1[CH:44]=[CH:43][C:38]2[O:39][CH2:40][CH2:41][O:42][C:37]=2[C:36]=1[CH3:45])=[O:34])[C:27]([CH3:30])([CH3:28])[CH3:29])[CH3:25]

Participants

8

Reactant 4

HCID 1363632,2-Dimethyl-3-pentanoneHCID 5003444Sodium cyanoborohydrideHCID 598386535-Methyl-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid (1-ethyl-2,2-dimethyl-propylidene) hydrazideHCID 131727201HCID 131727201, compound

Product 1

HCID 598386235-Methyl-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid n'-(1-ethyl-2,2-dimethyl-propyl)-hydrazide

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 176Acetic AcidSolventHCID 702EthanolSolvent

Procedure

0.86 g (4.1 mmol) of -methyl-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid hydrazide and 1.14 g (10 mmol) of 2,2 dimethyl pentan-3-one, 30 mL of ethyl alcohol and 20 drops of glacial acetic acid were refluxed for 6 hours. TLC indicated ca. a 60% conversion to 5-methyl-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid (1-ethyl-2,2-dimethyl-propylidene)-hydrazide (Rf=0.40, 1:1 ethyl acetate:hexane). The reaction was cooled, 3 mL of glacial acetic acid followed by 0.63 g (10 mmol) of sodium cyanoborohydride were added, and the reaction was stirred at room temperature for 3 hours. Most of the alcohol was removed on a rotary evaporator. 30 mL of water was added, followed by the addition of 10% NaOH/H2O until the reaction mixture was basic. The mixture was extracted extensively with ethyl acetate. The ethyl acetate extract was dried and evaporated to give 1.2 g of crude material. The product was purified by column chromatography on silica gel, eluting with 20-30% ethyl acetate/hexane. About 0.46 g of pure 5-methyl-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid N′-(1-ethyl-2,2-dimethyl-propyl)-hydrazide was obtained. TLC: Rf=0.46 (1:1 ethyl acetate:hexane). 1H NMR (CDCl3, 500 MHz) δ (ppm): 7.1 (br, 1H[NH]), 6.85 (d, 1H), 6.71 (d, 1H), 4.8 (br, 1H), 4.29 (m, 2H), 4.25 (m, 2H), 2.4 (m, 1H), 2.29 (s, 3H), 1.7 (m, 1H), 1.3 (m, 1H), 1.15 (t, 3H), 0.98 (s, 9H).

Workup

  1. temperatureThe reaction was cooled
  2. additionwere added
  3. customMost of the alcohol was removed on a rotary evaporator
  4. addition30 mL of water was added
  5. additionfollowed by the addition of 10% NaOH/H2O until the reaction mixture
  6. extractionThe mixture was extracted extensively with ethyl acetate
  7. extractionThe ethyl acetate extract
  8. customwas dried
  9. customevaporated
  10. customto give 1.2 g of crude material
  11. customThe product was purified by column chromatography on silica gel
  12. washeluting with 20-30% ethyl acetate/hexane

Sources & evidence

ORD record
ord-92ae6a6a530a421d8d7b60f275e16b92
Source dataset
uspto-grants-2016_06
Patent number
US09359289B2

Reaction notes

Loading…