Sodium hydride → 5-Bromo-4-(cyclopropylmethoxy)-2-methoxypyridine

HRID 575807Notes

Reaction equation

[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.[H-].[Na+].[Br:8][C:9]1[C:10](Cl)=[CH:11][C:12]([O:15][CH3:16])=[N:13][CH:14]=1>C1COCC1.[NH4+]>[Br:8][C:9]1[C:10]([O:5][CH2:4][CH:1]2[CH2:3][CH2:2]2)=[CH:11][C:12]([O:15][CH3:16])=[N:13][CH:14]=1

Participants

Conditions

Temperature: 20 °C

Procedure

To a solution of cyclopropylmethanol (446 mg, 6.18 mmol) in THF (10 mL) was added NaH (247 mg, 6.18 mmol, 60% in mineral oil) in one portion at 0° C. The reaction mixture was warmed up to 20° C. over a period of 30 mins and stirred at 20° C. for 10 mins. Then 5-bromo-4-chloro-2-methoxypyridine (550 mg, 2.47 mmol) was added in one portion and the mixture was stirred at 70° C. for 4 hours. The mixture was diluted with saturated ammonium aqueous solution (50 mL) and extracted by EtOAc (2×30 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated to give the crude product which was purified by silica gel column chromatography (PE:EA=20:1 to 10:1) to afford the title compound (450 mg, 70.6%) as colorless oil. 1H NMR: (CDCl3, 400 MHz) δ: 8.11 (s, 1H), 6.18 (s, 1H), 3.90 (s, 3H), 3.89-3.88 (m, 2H), 1.39-1.27 (m, 1H), 0.70-0.67 (m, 2H), 0.46-0.43 (m, 2H). LCMS (M+H)+=258.0 (M+1)+; 260.0

Workup

stirringthe mixture was stirred at 70° C. for 4 hours
extractionextracted by EtOAc (2×30 mL)
dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
filtrationfiltered
concentrationconcentrated
customto give the crude product which
customwas purified by silica gel column chromatography (PE:EA=20:1 to 10:1)

Sources & evidence

ORD record: ord-107cb98c0c1745d49860aeefb8d8f169
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09034900B2

Reaction notes

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