Sodium Bicarbonate → 3-(1-benzyl-1H-pyrazol-4-yl)-2-chloropyridine

HRID 883025Notes

Reaction equation

[CH2:1]([N:8]1[CH:12]=[C:11](I)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:14][C:15]1[C:20](B(O)O)=[CH:19][CH:18]=[CH:17][N:16]=1.C(=O)(O)[O-].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([N:8]1[CH:12]=[C:11]([C:20]2[C:15]([Cl:14])=[N:16][CH:17]=[CH:18][CH:19]=2)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 85 °C

Procedure

1-Benzyl-4-iodo-1H-pyrazole (1.35 g, 4.77 mmol), 2-chloropyridin-3-ylboronic acid (1.50 g, 9.53 mmol), sodium bicarbonate (1.20 g, 14.3 mmol) and Pd(PPh3)4 (276 mg, 0.239 mmol) were combined in an argon-purged sealed tube. Dimethoxyethane (8 mL) and water (5 mL) were added and the mixture was heated to 85° C. for 16 hours. The reaction was cooled to rt, diluted with water and extracted into EtOAc. The separated organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. This residue was purified by silica gel chromatography (50-75% EtOAc/hexanes) to yield 3-(1-benzyl-1H-pyrazol-4-yl)-2-chloropyridine as a light yellow oil after concentration. MS m/z=270 [M+1]+. Calc'd for C15H12FN3: 269.74.

Workup

custompurged
customsealed tube
additionDimethoxyethane (8 mL) and water (5 mL) were added
temperatureThe reaction was cooled to rt
additiondiluted with water
extractionextracted into EtOAc
dry with materialThe separated organic layer was dried over anhydrous sodium sulfate
filtrationfiltered
concentrationconcentrated
customThis residue was purified by silica gel chromatography (50-75% EtOAc/hexanes)

Sources & evidence

ORD record: ord-2a1f22fc0bae4191895be2d94dc9f531
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08236823B2

Reaction notes

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