1,2-Dichloroethane → (Z)-N-(3-(3,4-dichlorophenyl)propyl)-2-(2,2-dimethyl-5-oxo-1,3-dioxolan-4-ylidene)acetamide

HRID 1848371Notes

Reaction equation

HRID 1848371 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][CH2:10][CH2:11][NH2:12])[CH:5]=[CH:6][C:7]=1[Cl:8].[CH3:13][C:14]1([CH3:24])[O:18]/[C:17](=[CH:19]\[C:20](O)=[O:21])/[C:16](=[O:23])[O:15]1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][CH2:10][CH2:11][NH:12][C:20](=[O:21])/[CH:19]=[C:17]2\[O:18][C:14]([CH3:13])([CH3:24])[O:15][C:16]\2=[O:23])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 11636888Z-2,2-dimethyl-5-carboxymethylene-1,3-dioxolan-4-oneHCID 227290393-(3,4-Dichlorophenyl)propan-1-amine

Product 1

HCID 21947512(Z)-N-(3-(3,4-dichlorophenyl)propyl)-2-(2,2-dimethyl-5-oxo-1,3-dioxolan-4-ylidene)acetamideYield 90.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a cold (0° C.) solution of the hydrochloride salt of Intermediate 1 (7.1 g, 30 mmol), (Z)-2-(2,2-dimethyl-5-oxo-1,3-dioxolan-4-ylidene)acetic acid (5.6 g, 33 mmol), EDC (6.8 g, 36 mmol), and HOBt (5.4 g, 36 mmol) in DMF (200 mL) was added N-methylmorpholine (13 mL, 120 mmol). The reaction mixture was allowed to warm to rt, stirred for 16 h, diluted with EtOAc (500 mL), the solution washed with saturated aqueous NaCl:water (1:1), and the organic portion dried over MgSO4, filtered and evaporated to dryness in vacuo. The product was purified by silica gel chromatography (330 g silica gel) to obtain 9.68 g (89%) of Intermediate 5. HPLC/MS (Method C) RT=3.40 min; [M+H]+ 359; 1H NMR (500 MHz, chloroform-d) (δ ppm): 1.76 (s, 6H), 1.88 (quin, J=7.42 Hz, 2H), 2.64 (t, 2H), 3.37 (q, 2H), 5.86 (s, 1H), 6.37 (br. s., 1H), 7.01-7.07 (m, 1H), 7.28 (d, 1H), 7.35 (d, J=7.70 Hz, 1H).

Workup

  1. washthe solution washed with saturated aqueous NaCl:water (1:1)
  2. dry with materialthe organic portion dried over MgSO4
  3. filtrationfiltered
  4. customevaporated to dryness in vacuo
  5. customThe product was purified by silica gel chromatography (330 g silica gel)

Sources & evidence

ORD record
ord-bfe2b49a85024911814bda9f3fc6f68d
Source dataset
uspto-grants-2015_02
Patent number
US08952180B2

Reaction notes

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