Dimethylformamide → HCID 18474278, compound

HRID 1976098Notes

Reaction equation

HRID 1976098 reaction equation
Cl.[Cl:2][C:3]1[CH:24]=[CH:23][CH:22]=[CH:21][C:4]=1[O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH2:14][CH:15]2[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)[CH:8]=1.CN(C)C=[O:28].[CH:30]([N:33](CC)C(C)C)(C)[CH3:31].Cl.C(=N)(OCC)C>>[C:14]([OH:28])(=[O:13])[CH3:15].[Cl:2][C:3]1[CH:24]=[CH:23][CH:22]=[CH:21][C:4]=1[O:5][CH2:6][C:7]1[CH:8]=[C:9]([O:13][CH2:14][CH:15]2[CH2:16][CH2:17][N:18]([C:30](=[NH:33])[CH3:31])[CH2:19][CH2:20]2)[CH:10]=[CH:11][CH:12]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 2724290Ethanimidic acid, ethyl ester, hydrochloride (1:1)HCID 18474273HCID 18474273, compound

Product 1

HCID 18474278HCID 18474278, compound

Procedure

To 40 mg (0.109 mmol) of 1-[(2-chlorophenoxy)methyl-]-3-[(piperidin-4-yl)methoxy]benzene hydrochloride as prepared in the preceding step, in 1 mL of N,N-dimethylformamide containing 100 μL (0.908 mmol) of N,N-diisopropylethylamine was added 40 mg (0.325 mmol) of ethyl acetimidate hydrochloride. The reaction mixture was stirred at ambient temperature for 3 days. The reaction mixture was concentrated in vacuo and the residue was quenched with 1 N sodium hydroxide, extracted into methylene choride, dried (K2CO3), and concentrated. The residue was dissolved with 1 mL of methylene chloride and then treated with 500 μL of glacial acetic acid. The solution was then applied directly to preparative thin layer chromatography using methylene chloride/methanol/glacial acetic (83:15:2) as developing solvent to provide 33.8 mg of the title compound as a gum. 1H-NMR (300 MHz, DMSO-d6) δ 7.45 (dd, 1 H, J=1.5, 7.9 Hz), 7.27-7.34 (m, 2 H), 7.20-7.23 (dd, 1 H, J=1.4, 8.3 Hz), 6.89-7.04 (m, 4 H), 5.76 (s, 2 H), 4.07 (d, 2 H, J=14 Hz), 3.87 (d, 2 H, J=6.2 Hz), 3.05 (t, 2 H, J=13 Hz), 2.22 (s, 3 H), 2.05-2.13 (m, 1 H), 1.85 (d, 2 H), 1.71 (br s, 3 H), and 1.18-1.38 (m, 2 H). Mass spectrum (MALDI-TOF; α-cyano-4-hydroxycinnamic acid matrix matrix) calcd. for C21H25N2O2: 373.2 (M+H). Found: 373.0.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue was quenched with 1 N sodium hydroxide
  3. extractionextracted into methylene choride
  4. dry with materialdried (K2CO3)
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved with 1 mL of methylene chloride
  7. additiontreated with 500 μL of glacial acetic acid

Sources & evidence

ORD record
ord-70653748abe946738c0b00cbe7b351ed
Source dataset
uspto-grants-2001_05
Patent number
US06225302B1

Reaction notes

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