Acetic Acid → (E)-ethyl 2-(4-(2-(3-(diethoxyphosphoryl)-3,3-difluoropropoxy)ethoxy)-2-methoxybenzylidene)-3-oxobutanoate

HRID 629944Notes

Reaction equation

[F:1][C:2]([P:20](=[O:27])([O:24][CH2:25][CH3:26])[O:21][CH2:22][CH3:23])([F:19])[CH2:3][CH2:4][O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]=O)=[C:11]([O:17][CH3:18])[CH:10]=1.N1CCCCC1.C(O)(=O)C.[C:38]([O:44][CH2:45][CH3:46])(=[O:43])[CH2:39][C:40]([CH3:42])=[O:41]>C1(C)C=CC=CC=1>[CH2:22]([O:21][P:20]([C:2]([F:19])([F:1])[CH2:3][CH2:4][O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12](/[CH:15]=[C:39](\[C:40](=[O:41])[CH3:42])/[C:38]([O:44][CH2:45][CH3:46])=[O:43])=[C:11]([O:17][CH3:18])[CH:10]=1)([O:24][CH2:25][CH3:26])=[O:27])[CH3:23]

Participants

Conditions

Temperature: 110 °C

Procedure

To a solution of diethyl (1,1-difluoro-3-(2-(4-formyl-3-methoxyphenoxy)ethoxy)propyl)phosphonate (1 equiv.) in toluene (0.50 M) was added piperidine (0.10 equiv.), acetic acid (0.50 equiv.) and ethyl acetoacetate (1.2 equiv.). The reaction mixture was then heated to 110° C. for 18 h. At this point additional piperidine (0.10 equiv.), acetic acid (0.50 equiv.) and ethyl acetoacetate (0.50 equiv.) were added to the reaction mixture and heating at 110° C. was continued for 4 h. At this point the reaction mixture was allowed to cool to room temperature and the volatiles were removed in vacuo. The resulting residue was purified by a COMBIFLASH™ system using a gradient of 0-5% MeOH/DCM to provide the title compound (78%) as a solid.

Workup

temperatureheating at 110° C.
temperatureto cool to room temperature
customthe volatiles were removed in vacuo
customThe resulting residue was purified by a COMBIFLASH™ system

Sources & evidence

ORD record: ord-350716e026854e5d90d7adcdd8214465
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09315530B2

Reaction notes

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