Ethyl Acetate → racemic 2,6-difluoro-N-[(1R,2R,3R)-2-(4-fluorophenyl)-3-methyl-cyclopropyl]benzamide

HRID 1479159Notes

Reaction equation

[Na].S(N[N:13]=[CH:14][C:15]1[CH:20]=CC=C[C:16]=1[C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1)(C1C=CC(C)=CC=1)(=O)=O.[F:28][C:29]1[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[C:30]=1[C:31](N/C=C\C)=[O:32].O1CCOCC1.CCOC(C)=O>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O.[Rh+2].[Rh+2].O>[F:28][C:29]1[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[C:30]=1[C:31]([NH:13][C@@H:14]1[C@H:15]([CH3:20])[C@@H:16]1[C:21]1[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=1)=[O:32]

Participants

Conditions

Temperature: 75 °C

Procedure

4-Fluorophenyl benzaldehyde-tosylhydrazone sodium salt from example P2b (261 mg, 0.832 mmol), 2,6-difluoro-N—[(Z)-prop-1-enyl]benzamide (164 mg, 832 mmol), benzyltriethylammonium chloride (18.6 mg, 0.083 mmol), and rhodium acetate dimer (3.6 mg, 0.0083 mmol) were stirred with dioxane (6 ml) to give a thick slurry. This was heated at 75° C. for 4 hours. The mixture was shaken between EtOAc and water. The organic phase was dried with MgSO4 and evaporated to yield 230 mg of a crude mixture. This was chromatographed on silica with EtOAc/cyclohexane to yield 26 mg (10%) of racemic 2,6-difluoro-N-[(1R,2R,3R)-2-(4-fluorophenyl)-3-methyl-cyclopropyl]benzamide. M.p. 90-96° C.

Workup

customto give a thick slurry
dry with materialThe organic phase was dried with MgSO4
customevaporated
customto yield 230 mg of a crude mixture
customThis was chromatographed on silica with EtOAc/cyclohexane

Sources & evidence

ORD record: ord-39c2a098a324480f93b167f44fd367f1
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09408392B2

Reaction notes

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