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

HRID 920797Notes

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

To a suspension of NaH (0.733 g, 18.32 mmol, 60% in mineral oil) in DMF (14 mL) was added 2-(4-bromophenyl)acetonitrile (1.796 g, 9.16 mmol) followed by 1,3-dibromo-2,2-dimethoxypropane (2.0 g, 7.64 mmol) and the reaction mixture was heated to 60° C. and stirred for 12 h. The reaction mixture was cooled to RT, poured into water (150 mL) and extracted with EtOAc (3×40 mL). The combined organic layer was washed with brine, dried over Na2SO4, filtered and the filtrate concentrated. The crude product was purified by silica gel chromatography (24 g REDISEP® column, eluting with 5% EtOAc in hexane). Fractions containing the product were combined and evaporated to afford Intermediate 314A as a white solid (2 g, 88%). 1H NMR (300 MHz, DMSO-d6) δ ppm 7.68-7.57 (m, 2H), 7.46-7.40 (m, 2H), 3.18 (s, 3H), 3.08 (s, 1H), 3.07 (s, 3H), 3.05-3.02 (m, 1H), 2.74-2.71 (m, 1H), 2.70-2.67 (m, 1H).

Workup

temperatureThe reaction mixture was cooled to RT
extractionextracted with EtOAc (3×40 mL)
washThe combined organic layer was washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationthe filtrate concentrated
customThe crude product was purified by silica gel chromatography (24 g REDISEP® column, eluting with 5% EtOAc in hexane)
additionFractions containing the product
customevaporated

Sources & evidence

ORD record: ord-393105327b2544ba841a568df9a63589
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09273058B2

Reaction notes

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