Hydrochloric Acid → HCID 58042516, compound

HRID 2048036Notes

Reaction equation

[H-].[Na+].[F:3][C:4]1([F:10])[CH2:7][CH:6]([CH2:8][OH:9])[CH2:5]1.Cl[C:12]1[C:17]([Cl:18])=[CH:16][CH:15]=[CH:14][N:13]=1.Cl>C1COCC1>[Cl:18][C:17]1[C:12]([O:9][CH2:8][CH:6]2[CH2:7][C:4]([F:10])([F:3])[CH2:5]2)=[N:13][CH:14]=[CH:15][CH:16]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Sodium hydride (60% dispersion in mineral oil, 1.017 g, 70.6 mmol) was suspended in THF (30.0 mL) and the reaction was cooled to 0° C. under nitrogen with an ice bath. (3,3-Difluorocyclobutyl)methanol (Preparation 2, 2.95 g, 24.2 mmol) in THF (30 mL) was added dropwise to the mixture maintaining the temperature at 0° C. After stirring for 30 minutes, 2,3-dichloropyridine (3.25 g, 22.0 mmol) was added and the suspension was heated to reflux for 16 hours. An aqueous solution of HCl (1.0M, 20 mL) was added and the reaction was extracted with EtOAc (2×100 mL). The combined organics were then dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (Biotage®, gradient of 0-50% EtOAc in heptane,) to afford the title compound (4.82 g, 85%):

Workup

temperaturemaintaining the temperature at 0° C
temperaturethe suspension was heated
temperatureto reflux for 16 hours
extractionthe reaction was extracted with EtOAc (2×100 mL)
dry with materialThe combined organics were then dried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by silica gel chromatography (Biotage®, gradient of 0-50% EtOAc in heptane,)

Sources & evidence

ORD record: ord-d4de9b5ad40049fabe768125b309fc56
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08592629B2

Reaction notes

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