Sodium Hydroxide → 2-Amino-5-[(3,5-difluorobenzyl)oxy]benzonitrile

HRID 1803841Notes

Reaction equation

S(S([O-])=O)([O-])=O.[Na+].[Na+].[F:9][C:10]1[CH:11]=[C:12]([CH:26]=[C:27]([F:29])[CH:28]=1)[CH2:13][O:14][C:15]1[CH:16]=[CH:17][C:18]([N+:23]([O-])=O)=[C:19]([CH:22]=1)[C:20]#[N:21].[OH-].[Na+]>O.[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.ClCCl>[NH2:23][C:18]1[CH:17]=[CH:16][C:15]([O:14][CH2:13][C:12]2[CH:26]=[C:27]([F:29])[CH:28]=[C:10]([F:9])[CH:11]=2)=[CH:22][C:19]=1[C:20]#[N:21]

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 85% sodium hydrosulfite (38.1 g, 186 mmol) in water (200 mL) was added dropwise to a mixture of 5-[(3,5-difluorobenzyl)oxy]-2-nitrobenzonitrile (9 g, 31 mmol) and tetrabutylammonium chloride (5.86 g, 21.1 mmol) in dichloromethane (200 mL) under vigorous stirring. After 2 hours, the reaction mixture was cooled at 0° C. and 2N NaOH (200 mL) was added to reach a pH value of 12. The organic phase was separated and the acqueous layer was washed with dichloromethane. Organic phases were collected and treated for 3 hours with 4M hydrochloric acid in dioxane (50 mL). The reaction mixture was washed with water, NaHCO3 saturated solution and brine. Organic phase was dried over sodium sulphate, filtered and evaporated to dryness affording 7.6 g (yield 94%) of the title compound.

Workup

customThe organic phase was separated
washthe acqueous layer was washed with dichloromethane
customOrganic phases were collected
additiontreated for 3 hours with 4M hydrochloric acid in dioxane (50 mL)
washThe reaction mixture was washed with water, NaHCO3 saturated solution and brine
dry with materialOrganic phase was dried over sodium sulphate
filtrationfiltered
customevaporated to dryness

Sources & evidence

ORD record: ord-15deb4b7c5314fd0b1420dc1ff1752db
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08354399B2

Reaction notes

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