1,1,3-Trimethoxypropane → 7-Amino-5-cyano-8-methylquinoline

HRID 1416901Notes

Reaction equation

[C:1]([C:3]1[CH:8]=[C:7]([NH2:9])[C:6]([CH3:10])=[C:5]([NH2:11])[CH:4]=1)#[N:2].CO[CH:14](OC)[CH2:15][CH2:16]OC>C(O)C.O.[OH-].[NH4+].[Cl-].[Zn+2].[Cl-]>[NH2:11][C:5]1[C:6]([CH3:10])=[C:7]2[C:8]([CH:14]=[CH:15][CH:16]=[N:9]2)=[C:3]([C:1]#[N:2])[CH:4]=1

Participants

Conditions

Temperature: 65 °C

Procedure

A mixture of 4-cyano-2,6-diaminotoluene (3.56 g), ferric chloride hexahydrate (11.63 g), and zinc chloride (0.499 g) in ethanol (600 mL) is heated to 65° C. A solution of 1,1,3-trimethoxypropane (5.23 g) in ethanol (90 mL) is added dropwise via syringe pump over a period of 90 minutes. The reaction is then heated to reflux for 2.5 hours. The reaction is cooled to room temperature and the solvent rotary evaporated. The residue is diluted with 300 mL of water and basified to pH=11 with concentrated ammonium hydroxide. The products are extracted with ethyl acetate (4×300 mL), and the combined extracts dried over sodium sulfate and rotary evaporated. The residue is purified by flash chromatography on silica gel, eluting with 50% ethyl acetate/hexanes to afford 7-amino-5-cyano-8-methylquinoline as a yellow solid.

Workup

temperatureThe reaction is then heated
temperatureto reflux for 2.5 hours
temperatureThe reaction is cooled to room temperature
extractionThe products are extracted with ethyl acetate (4×300 mL)
dry with materialthe combined extracts dried over sodium sulfate and rotary evaporated
customThe residue is purified by flash chromatography on silica gel
washeluting with 50% ethyl acetate/hexanes

Sources & evidence

ORD record: ord-059e6e0e77084274963b69de1596d71f
Source dataset: uspto-grants-1999_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05916900

Reaction notes

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