Acetic Acid → HCID 19595165, compound

HRID 612472Notes

Reaction equation

HRID 612472 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5](OC)=[C:6]([CH2:8][CH2:9][N:10]([C:12]2C=CN=CC=2)[NH2:11])[CH:7]=1.C[O:21][CH2:22]Cl.[OH-].[Na+].[C:26](O)(=O)[CH3:27]>>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:7]=1[CH2:12][N:10]([NH:11][C:27]1[CH:26]=[CH:12][N:10]=[CH:9][CH:8]=1)[CH2:9][CH:8]2[O:21][CH3:22]

Participants

5

Reactant 4

HCID 176Acetic AcidHCID 7864Chloromethyl Methyl EtherHCID 14798Sodium HydroxideHCID 19595144HCID 19595144, compound

Product 1

HCID 19595165HCID 19595165, compoundYield 52%

Conditions

Temperature
0 °C

Procedure

Lithium aluminum hydride (3.3 g) was added portionwise to a suspension of N-[2-(5-chloro-2-methoxyphenyl)ethylidine]-N-pyridin-4-ylhydrazine hydrochloride (13.4 g) in tetrahydrofuran (215 mL) at 0° C. The reaction mixture was stirred at ambient temperature for 2 hrs, and sodium sulfate decahydrate was added. The mixture was filtered, and the filtrate was concentrated to provide 11.8 g of N-[2-(5-chloro-2-methoxyphenyl)ethyl]-N-pyridine-4-ylhydrazine, as an oil. A solution of N-[2-(5-chloro-2-methoxyphenyl)ethyl]-N-pyridine-4-ylhydrazine (11.8 g) and chloromethyl methyl ether (3.8 g) in acetic acid (170 mL) was heated under reflux for 2 hrs and then cooled to 0° C. Sodium hydroxide solution (50%) was added, and the mixture was extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The residue was chromatographed on silica gel, eluting with 10% methanol/ethyl acetate. The appropriate fractions were collected and concentrated to provide 6.54 g (52%) of product. Recrystallization from ethyl acetate provided the analytical sample, mp 152-154° C. (dec).

Workup

  1. temperatureunder reflux for 2 hrs
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe combined organic layers were washed with water and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated
  7. customThe residue was chromatographed on silica gel
  8. washeluting with 10% methanol/ethyl acetate
  9. customThe appropriate fractions were collected
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-263444bc94f144faba64f1171443e1b1
Source dataset
uspto-grants-1999_12
Patent number
US06004977

Reaction notes

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