Dimethyl Sulfoxide → 2-(3-Chloro-5-formyl-pyridin-2-yl)-2-methyl-propionitrile

HRID 2387116Notes

Reaction equation

C(Cl)(=O)C(Cl)=O.CS(C)=O.[Cl:11][C:12]1[C:13]([C:20]([CH3:24])([CH3:23])[C:21]#[N:22])=[N:14][CH:15]=[C:16]([CH2:18][OH:19])[CH:17]=1.C(N(CC)CC)C>C(Cl)Cl.O>[Cl:11][C:12]1[C:13]([C:20]([CH3:24])([CH3:23])[C:21]#[N:22])=[N:14][CH:15]=[C:16]([CH:18]=[O:19])[CH:17]=1

Participants

Conditions

Temperature: -50 °C

Procedure

A solution of oxalyl chloride (0.45 mL, 5.21 mmol) and in dry CH2Cl2 (11 mL), was cooled to −50° C. Dimethyl sulfoxide (0.76 g, 10.87 mmol) was added drop wise at a rapid rate. After 5 minutes, 2-(3-chloro-5-hydroxymethyl-pyridin-2-yl)-2-methyl-propionitrile (0.95 g, 4.53 mmol) from step 1 above, in dry CH2Cl2 (5 mL) was added via cannula followed by triethylamine (3.16 g, 22.65 mmol). The reaction was stirred at −50° C. for 30 additional minutes and then allowed to reach room temperature. The reaction was poured into water (150 mL) and extracted with EtOAc (2×50 mL). The combined organics were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography (0-20% EtOAc in hexanes) to give the product (0.58 g, 62% yield) as a clear oil. 1H NMR (400 MHz, CDCl3): δ 1.90 (s, 6 H), 8.20 (s, 1 H), 8.93 (s, 1H), 10.12 (s, 1 H). ESIMS (MH+): 209.

Workup

customto reach room temperature
extractionextracted with EtOAc (2×50 mL)
washThe combined organics were washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified by flash column chromatography (0-20% EtOAc in hexanes)

Sources & evidence

ORD record: ord-ae893e30e111402ea72666f2d4973077
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08268835B2

Reaction notes

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