Sodium Iodide → Diethyl (1,1-difluoro-3-(2-(4-formyl-3-methoxyphenoxy)ethoxy)propyl)phosphonate

HRID 629943Notes

Reaction equation

[OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[C:4]([O:10][CH3:11])[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[Na+].Br[CH2:21][CH2:22][O:23][CH2:24][CH2:25][C:26]([P:29](=[O:36])([O:33][CH2:34][CH3:35])[O:30][CH2:31][CH3:32])([F:28])[F:27]>CN(C=O)C.O.CCOC(C)=O>[F:28][C:26]([P:29](=[O:36])([O:33][CH2:34][CH3:35])[O:30][CH2:31][CH3:32])([F:27])[CH2:25][CH2:24][O:23][CH2:22][CH2:21][O:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[C:4]([O:10][CH3:11])[CH:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 4-hydroxy-2-methoxybenzaldehyde (1 equiv.) in DMF (0.25 M) was added cesium carbonate (2 equiv.), sodium iodide (0.20 equiv.) and diethyl (3-(2-bromoethoxy)-1,1-difluoropropyl)phosphonate (1.2 equiv.) (described in ref. 88, Ex 7 Step 1). The reaction mixture was stirred at 100° C. for 3 h, after which it was allowed to cool to room temperature. The resulting mixture was then diluted with water and EtOAc. This mixture was transferred to a separatory funnel and washed with water three times. The organic layer was then separated, dried over anhydrous Na2SO4 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 (79%) as a solid.

Workup

temperatureto cool to room temperature
customThis mixture was transferred to a separatory funnel
washwashed with water three times
customThe organic layer was then separated
dry with materialdried over anhydrous Na2SO4
customthe volatiles were removed in vacuo
customThe resulting residue was purified by a COMBIFLASH™ system

Sources & evidence

ORD record: ord-39f00b24ac414ab3a54c9cc403b2627a
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09315530B2

Reaction notes

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