Sodium hydride → HCID 67301756, compound

HRID 1015417Notes

Reaction equation

[OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1.[H-].[Na+].[F:19][C:20]1[CH:27]=[CH:26][CH:25]=[C:24](F)[C:21]=1[C:22]#[N:23]>CN(C)C=O>[C:13]([O:12][C:10]([N:7]1[CH2:8][CH2:9][N:4]([CH2:3][CH2:2][O:1][C:24]2[CH:25]=[CH:26][CH:27]=[C:20]([F:19])[C:21]=2[C:22]#[N:23])[CH2:5][CH2:6]1)=[O:11])([CH3:16])([CH3:15])[CH3:14]

Participants

Conditions

Temperature: 40 °C

Procedure

t-butyl 4-(2-hydroxyethyl)piperazine-1-carboxylate (0.6 g; 2.6 mmol) was added to a suspension of sodium hydride (125 mg; 3.1 mmol) in 5 mL of anhydrous dimethylformamide at 0° C. Mixture was then heated to 40° C. for 2 hours. Anion was cooled to room temperature and added to a 0° C. mixture of 2,6-difluorobenzonitrile in 5 mL of dimethylformamide. After 16 hours at room temperature, reaction was quenched over 20 g of ice, mixture was extracted 4×50 mL with ethyl acetate. Combined organics was washed with 6×40 mLs water, brine and dried over MgSO4. Crude oil was obtained after filtration and concentration. Material was purified by flash chromatography using 2-3.5% methanol/dichloromethane gradient to obtain 660 mg of title compound. (73% yield).

Workup

temperatureAnion was cooled to room temperature
additionadded to a 0° C.
customreaction
customwas quenched over 20 g of ice, mixture
extractionwas extracted 4×50 mL with ethyl acetate
washCombined organics was washed with 6×40 mLs water, brine
dry with materialdried over MgSO4
customCrude oil was obtained
filtrationafter filtration and concentration
customMaterial was purified by flash chromatography

Sources & evidence

ORD record: ord-8fdf45afa1494215bf34e328339f2e69
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07985755B2

Reaction notes

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