Dimethyl malonate → HCID 67070938, compound

HRID 732059Notes

Reaction equation

HRID 732059 reaction equation
Cl[CH:2]([C:4]1[O:5][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([Cl:15])[CH:10]=2)=[N:7][N:8]=1)[CH3:3].[C:16]([O:23][CH3:24])(=[O:22])[CH2:17][C:18]([O:20][CH3:21])=[O:19].C1CCN2C(=NCCC2)CC1>C(#N)C.ClCCl>[CH3:21][O:20][C:18](=[O:19])[CH:17]([CH:2]([C:4]1[O:5][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([Cl:15])[CH:10]=2)=[N:7][N:8]=1)[CH3:3])[C:16]([O:23][CH3:24])=[O:22]

Participants

6

Reactant 3

HCID 7943Dimethyl malonateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 4962682HCID 4962682, compound

Product 1

HCID 67070938HCID 67070938, compoundYield 77.5%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

2-(1-Chloro-ethyl)-5-(3-chloro-phenyl)-[1,3,4]oxadiazole (331 mg, 1.36 mmol) was mixed with dimethyl malonate (360 mg, 2/76 mmol) and DBU (207 mg, 1.36 mmol) in acetonitrile (3 ml) at 70° C. overnight. The reaction mixture was dilute with dichloromethane and washed with water. The organic layer was dried and concentrated. The residue was purified with 5˜20% ethyl acetate in hexanes to give 357 mg (74.3%) 2-{1-[5-(3-Chloro-phenyl)-[1,3,4]oxadiazol-2-yl]-ethyl}-malonic acid dimethyl ester as white solid. 1H-NMR(CDCl3) d(ppm): 8.03 (s, 1H), 7.95 (d, 1H), 7.53 (d, 1H), 7.47 (t, 1H), 4.06 (d, 1H), 3.95 (m, 1H), 3.84 (s, 3H), 3.74 (s, 3H) and 1.51 (d, 3H). Step 2: 3-[5-(3-Chloro-phenyl)-[1,3,4]oxadiazol-2-yl]-butyric acid methyl ester: 2-{1-[5-(3-Chloro-phenyl)-[1,3,4]oxadiazol-2-yl]-ethyl}-malonic acid dimethyl ester (352.8 mg, 1.0 mmol) was mixed with sodium chloride (76.3 mg, 1.3 mmol) and a drop of water in DMSO (1.5 ml) at 175° C. for an h. The reaction mixture was diluted with water and extracted with dichloromethane. The organic layer was washed with water and concentrated. The residue was purified with column chromatography with 10˜20% ethyl acetate in hexanes to give 215 mg (76.8%) 3-[5-(3-chloro-phenyl)-[1,3,4]oxadiazol-2-yl]-butyric acid methyl ester as clear oil.

Workup

  1. washwashed with water
  2. customThe organic layer was dried
  3. concentrationconcentrated
  4. customThe residue was purified with 5˜20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-e52bfbc5c19e4e2193d66ade2a706b2d
Source dataset
uspto-grants-2009_09
Patent number
US07585881B2

Reaction notes

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