Sodium hydride → 1-[4-(5-Bromo-4-chloro-pyridin-3-ylmethoxy)-piperidin-1-yl]-ethanone

HRID 712752Notes

Reaction equation

[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8](=[O:10])[CH3:9])[CH2:4][CH2:3]1.[H-].[Na+].[Br:13][C:14]1[CH:15]=[N:16][CH:17]=[C:18]([CH2:21]Br)[C:19]=1[Cl:20].[NH4+].[Cl-]>CN(C=O)C.CCOC(C)=O.O>[Br:13][C:14]1[C:19]([Cl:20])=[C:18]([CH2:21][O:1][CH:2]2[CH2:7][CH2:6][N:5]([C:8](=[O:10])[CH3:9])[CH2:4][CH2:3]2)[CH:17]=[N:16][CH:15]=1

Participants

Conditions

Temperature: 0 °C

Procedure

1-(4-Hydroxy-piperidin-1-yl)-ethanone (301 mg, 2.10 mmol) is dissolved in DMF (10 mL) and 60% sodium hydride in mineral oil (84 mg, 2.10 mmol) is added at 0° C. The mixture is stirred for 15 min at 0° C. and 3-bromo-5-bromomethyl-4-chloro-pyridine (300 mg, 1.05 mmol) is added at that temperature. Then the mixture is warmed up to room temperature and stirred for 1 hr. Saturated NH4Cl aqueous solution (15 mL) is added, along with water (50 mL) and EtOAc (50 mL). The mixture is stirred for 10 min and the aqueous layer is separated and extracted with EtOAc (2×50 ml). The organic layers are combined and concentrated to give the crude product. Purification by flash column chromatography affords 112 mg of 1-[4-(5-bromo-4-chloro-pyridin-3-ylmethoxy)-piperidin-1-yl]-ethanone.

Workup

temperatureThen the mixture is warmed up to room temperature
stirringstirred for 1 hr
stirringThe mixture is stirred for 10 min
customthe aqueous layer is separated
extractionextracted with EtOAc (2×50 ml)
concentrationconcentrated
customto give the crude product
customPurification by flash column chromatography

Sources & evidence

ORD record: ord-e83bef17b4fd4bc1b6a7d9ea609f1940
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181272B2

Reaction notes

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