Water → 1-(4-Bromophenyl)-3,3-dimethoxycyclobutanecarbonitrile

HRID 1509314Notes

Reaction equation

[H-].[Na+].[Br:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]#[N:12])=[CH:6][CH:5]=1.Br[CH2:14][C:15]([O:20][CH3:21])([O:18][CH3:19])[CH2:16]Br.O>CN(C=O)C>[Br:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2([C:11]#[N:12])[CH2:16][C:15]([O:20][CH3:21])([O:18][CH3:19])[CH2:14]2)=[CH:6][CH:5]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A suspension of sodium hydride (2 g, 50.0 mmol) in DMF (20 ml) was cooled to 0 degree before 2-(4-bromophenyl)acetonitrile (4 g, 20.40 mmol) was added slowly, The suspension was stirred at 0 degree for another 10 min before 1,3-dibromo-2,2-dimethoxypropane (2.62 g, 10.00 mmol) was added. The reaction mixture was stirred at 60° C. for 20 h before cooled to room temperature, poured into water (75 ml) and extracted with ethyl acetate (2×50 ml). The combined organic phase was washed with water (75 ml), brine (50 ml) and concentrated. The crude product was purified by column (100 g, biotage) eluted with ethyl acetate/cyclohexane (0-10%) to afford product 1.7 g (59% yield). 1H NMR (500 MHz, DMSO-d6): 7.46 (d, 2H), 7.29 (d, 2H), 3.21 (s, 3H), 3.11 (s, 3H), 3.03 (d, 2H), 2.62 (d, 2H).

Workup

additionwas added slowly
additionwas added
temperaturebefore cooled to room temperature
extractionextracted with ethyl acetate (2×50 ml)
washThe combined organic phase was washed with water (75 ml), brine (50 ml)
concentrationconcentrated
customThe crude product was purified by column (100 g, biotage)
washeluted with ethyl acetate/cyclohexane (0-10%)

Sources & evidence

ORD record: ord-5345c950359f4e8cb4ce88901cd06f04
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09221838B2

Reaction notes

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