Ethyl Acetate → (3-Amino-7,8-dihydro-naphtho[2,3-b]furan-2-yl)-(2,4-dichloro-phenyl)methanone

HRID 131170Notes

Reaction equation

HRID 131170 reaction equation
[OH:1][C:2]1[C:3]([C:12]#[N:13])=[CH:4][C:5]2[CH:6]=[CH:7][CH2:8][CH2:9][C:10]=2[CH:11]=1.[Cl:14][C:15]1[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:16]=1[C:17](=[O:20])[CH2:18]Cl.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CN(C)C=O.O>[NH2:13][C:12]1[C:3]2[CH:4]=[C:5]3[C:10]([CH2:9][CH2:8][CH:7]=[CH:6]3)=[CH:11][C:2]=2[O:1][C:18]=1[C:17]([C:16]1[CH:21]=[CH:22][C:23]([Cl:25])=[CH:24][C:15]=1[Cl:14])=[O:20]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 202502,2',4'-TrichloroacetophenoneHCID 218649383-Hydroxy-5,6-dihydro-naphthalene-2-carbonitrile

Product 1

HCID 21864965(3-Amino-7,8-dihydro-naphtho[2,3-b]furan-2-yl)-(2,4-dichloro-phenyl)methanoneYield 19%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 3-hydroxy-5,6-dihydro-naphthalene-2-carbonitrile from step 1 (100 mg, 0.58 mmol) and 2,4-dichlorophenacyl chloride (144 mg, 0.64 mmol, 1.1 eq) in anhydrous N,N-dimethylformamide (2 mL) was added potassium carbonate (161 mg, 1.2 mmol, 2 eq). The reaction mixture was shaken at 90° C. for 17 h. The mixture was cooled to room temperature and poured into ethyl acetate and water. Separated the organic phase and extracted the aqueous layer with ethyl acetate twice. Combined the ethyl acetate extracts and the original organic layer and evaporated in vacuo. The crude product was purified by HPLC and gave 39.4 mg (14% for two steps) of (3-Amino-7,8-dihydro-naphtho[2,3-b]furan-2-yl)-(2,4-dichloro-phenyl)-methanone as a brown oil. 1H-NMR (acetone-d6) δ 7.63 to 7.61 (m, 2H), 7.59 (s, 1H), 7.52 to 7.54 (m, 1H), 7.13 (s, 1H), 7.04 (broad, s, 2H), 6.59 (tt, J=10 Hz, 1.2 Hz, 1H), 6.07 (m, 1H), 2.92 (t, J=8.0 Hz, 2H), 2.33 (m, 2H); MS LC-MS (MH+=358.1/360.1); Rf=0.51, 30% ethyl acetate-hexane.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. customSeparated the organic phase
  3. extractionextracted the aqueous layer with ethyl acetate twice
  4. customthe original organic layer and evaporated in vacuo
  5. customThe crude product was purified by HPLC

Sources & evidence

ORD record
ord-ff7ff5d5680f4e2a9208efb463a79f2a
Source dataset
uspto-grants-2008_06
Patent number
US07384947B2

Reaction notes

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