tert-Butyl [(6-bromopyridin-3-yl)methyl]carbamate → HCID 67382216, compound

HRID 911662Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])=[CH:4][N:3]=1.[Br-].[CH:18]1([CH2:24][Zn+])[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1>C1COCC1.CCOC(C)=O>[C:13]([O:12][C:10]([NH:9][CH2:8][C:5]1[C:4]([CH2:24][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)=[N:3][CH:2]=[CH:7][CH:6]=1)=[O:11])([CH3:16])([CH3:15])[CH3:14]

Participants

Conditions

Temperature: 60 °C

Procedure

Dissolve 2-bromo-5-tert-butoxycarbonylaminomethyl-pyridine (500 mg, 1.74 mmol) in anhydrous THF (5 mL) in a sealed tube. Degas the solution, purge with nitrogen and add 1,1′-[bis(diphenylphosphino)ferrocene]dichloropalladium(II) (127 mg, 0.174 mmol) and 0.5M cyclohexylmethylzinc bromide in THF (10.4 mL, 5.22 mmol). Heat the mixture at 60° C. overnight. Cool to room temperature and dilute the reaction mixture with EtOAc. Add water and filter the precipitate over Celite®. Dry the organic phase over MgSO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel eluting with hexane and hexane/EtOAc (4:1, 3:2) to give the desired intermediate as an oil (359 mg, 68%). MS (ES+) m/z: 305 (M+H)+.

Workup

customDegas the solution
custompurge with nitrogen
temperatureCool to room temperature
filtrationAdd water and filter the precipitate over Celite®
dry with materialDry the organic phase over MgSO4
filtrationfilter
concentrationconcentrate in vacuo
customPurify the crude mixture by chromatography on silica gel eluting with hexane and hexane/EtOAc (4:1, 3:2)

Sources & evidence

ORD record: ord-709bed4507e24174a8c33ee360f97bd1
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08022062B2

Reaction notes

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