Ammonium Chloride → [1-(3-Bromo-phenyl)-1-difluoromethyl-allyl]carbamic acid tert-butyl ester

HRID 221685Notes

Reaction equation

[C:1]([O:5][C:6](=[O:19])[N:7]=[C:8]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([Br:18])[CH:13]=1)[CH:9]([F:11])[F:10])([CH3:4])([CH3:3])[CH3:2].[CH:20]([Mg]Br)=[CH2:21].[NH4+].[Cl-]>C1(C)C=CC=CC=1>[C:1]([O:5][C:6](=[O:19])[NH:7][C:8]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([Br:18])[CH:13]=1)([CH:9]([F:10])[F:11])[CH:20]=[CH2:21])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: -20 °C

Procedure

[1-(3-Bromo-phenyl)-2,2-difluoro-ethylidene]-carbamic acid tert-butyl ester (9.09 g, 27.2 mmol) was dissolved in toluene and cooled to −20° C. under N2. Using a syringe pump, vinylmagnesiumbromide (42.5 ml, 34.0 mmol) was added (1 eq. per hour). After 1.25 hrs no starting material was left and 218 ml half-saturated NH4Cl solution was added to the reaction. The product was extracted with TBME. The organic phases were washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by automated column chromatography (cyclohexane/TBME) to yield the title compound as a yellowish oil. 1H-NMR (600 MHz, DMSO-d6): 7.81 (br, 1H, NH), 7.52 (m, 2H), 7.35 (m, 2H), 6.48 (t, 1H, CHF2), 5.45 (d, 1H), 5.15 (d, 1H), 1.32 (s, 9H); MS: 362 [(M+H)+].

Workup

additionwas added (1 eq. per hour)
extractionThe product was extracted with TBME
washThe organic phases were washed with water and brine
dry with materialdried over Na2SO4
concentrationconcentrated under reduced pressure
customThe residue was purified by automated column chromatography (cyclohexane/TBME)

Sources & evidence

ORD record: ord-f839a9e75b354b8c990e3bb96c85c532
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08207164B2

Reaction notes

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