1-Butanol → HCID 22663351, compound

HRID 392213Notes

Reaction equation

HRID 392213 reaction equation
[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[C:6]([NH2:12])[CH:5]=1.Cl.C(O)CCC.[C:20]1(Cl)[C:26](=O)[C:25](Cl)=[C:24](Cl)[C:22](=O)[C:21]=1Cl>O1CCCC1.[Cl-].[Zn+2].[Cl-]>[CH3:1][O:2][C:3]([C:4]1[C:5]2[CH:26]=[CH:20][C:21]([CH2:22][CH2:24][CH3:25])=[N:12][C:6]=2[C:7]([O:10][CH3:11])=[CH:8][CH:9]=1)=[O:13]

Participants

7

Reactant 4

HCID 2631-Butanol2×HCID 313Hydrochloric AcidHCID 8371ChloranilHCID 2734814Methyl 3-Amino-4-methoxybenzoate

Product 1

HCID 22663351HCID 22663351, compoundYield 10.5%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Methyl-3-amino-4-methoxybenzoate (10.0 g) was treated with concentrated hydrochloric acid (14 ml) and n-butanol (10 ml), under nitrogen, with stirring. The stirred mixture was treated with p-chloranil (13.65 g) and then heated at reflux whilst a mixture of trans-2-hexanal (8 ml) and n-butanol (5 ml) was added dropwise over 2 hours using a syringe pump. After heating at reflux for a further 30 minutes the mixture was treated with a solution of anhydrous zinc chloride (7.52 g) in tetrahydrofuran (60 ml), then allowed to cool slowly to room temperature and then cooled to 0° C. for 18 hours. The reaction mixture was evaporated, then diluted with hydrochloric acid (1M) and then washed with diethyl ether. The pH of the solution was adjusted to 6 and the resulting emulsion was treated with ammonium hydroxide and the solution extracted with diethyl ether. The combined dark green extracts were dried over magnesium sulphate then evaporated. The resulting dark green oil was subjected to flash chromatography on silica eluting with a mixture of ethyl acetate and pentane (3:7, v/v) to give the title compound (1.5 g) as an orange oil. NMR(CDCl3): δ 9.36(d, J=8.9 Hz, 1H), 8.26(d, J=8.4 Hz, 1H), 7.47(d, J=8.9 Hz, 1H), 7.03(d, J=8.4 Hz, 1H), 4.14(s, 3H), 3.97(s, 3H), 3.02(m, 2H), 1.86(m, 2H), 1.03(t, J=7.3 Hz, 3H).

Workup

  1. temperatureheated
  2. temperatureat reflux whilst
  3. additionwas added dropwise over 2 hours
  4. temperatureAfter heating
  5. temperatureat reflux for a further 30 minutes the mixture
  6. temperaturecooled to 0° C. for 18 hours
  7. customThe reaction mixture was evaporated
  8. additiondiluted with hydrochloric acid (1M)
  9. washwashed with diethyl ether
  10. additionthe resulting emulsion was treated with ammonium hydroxide
  11. extractionthe solution extracted with diethyl ether
  12. dry with materialThe combined dark green extracts were dried over magnesium sulphate
  13. customthen evaporated
  14. additionThe resulting dark green oil was subjected to flash chromatography on silica eluting with a mixture of ethyl acetate and pentane (3:7, v/v)

Sources & evidence

ORD record
ord-ba687393a48447fab9e48df6d17b9a47
Source dataset
uspto-grants-2004_10
Patent number
US06800645B1

Reaction notes

Loading…