Stannous Chloride → tert-Butyl 1-(3-amino-4-chlorobenzyl)-2,2-difluorocyclopropanecarboxylate

HRID 1475628Notes

Reaction equation

[Cl:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][C:7]2([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:9][C:8]2([F:11])[F:10])=[CH:4][C:3]=1[N+:21]([O-])=O.[Sn](Cl)Cl.[F-].[K+]>O1CCOCC1.Cl>[NH2:21][C:3]1[CH:4]=[C:5]([CH:19]=[CH:20][C:2]=1[Cl:1])[CH2:6][C:7]1([C:12]([O:14][C:15]([CH3:18])([CH3:16])[CH3:17])=[O:13])[CH2:9][C:8]1([F:11])[F:10]

Participants

Conditions

Temperature: 70 °C

Procedure

1.60 g (4.60 mmol) of (+/−)-tert-butyl 1-(4-chloro-3-nitrobenzyl)-2,2-difluorocyclopropanecarboxylate were dissolved in 20 ml of dioxane, and 4.36 g (23.0 mmol) of tin(II) chloride and a few drops of 1 N hydrochloric acid were added at RT. The reaction mixture was heated at 70° C. for 1 h. After cooling to RT, 10 ml of 10% strength aqueous potassium fluoride solution were added. The mixture was extracted three times with ethyl acetate, and the combined organic phases were dried over magnesium sulphate and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 50:1→10:1). This gave 1.16 g of the target product (79.3% of theory).

Workup

temperatureAfter cooling to RT
extractionThe mixture was extracted three times with ethyl acetate
dry with materialthe combined organic phases were dried over magnesium sulphate
concentrationconcentrated under reduced pressure
customThe residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 50:1→10:1)

Sources & evidence

ORD record: ord-1ffbbb596b87490384a5f5e0ee0c88eb
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09018258B2

Reaction notes

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