Methylamine → (But-3-en-1-yl)(methyl)amine

HRID 650553Notes

Reaction equation

HRID 650553 reaction equation
[CH3:1][N:2]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3][CH2:4][CH:5]=[CH2:6].Br[C:15]1[CH:16]=[N:17][CH:18]=[C:19](SCC)[CH:20]=1.BrCCC=C.CN.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH3:1][N:2]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3][CH2:4][CH:5]=[CH2:6].[CH3:18][NH:17][CH2:16][CH2:15][CH:20]=[CH2:19]

Participants

8

Reactant 5

HCID 6329MethylamineHCID 11430Potassium CarbonateHCID 21241Homoallyl bromideHCID 18624577tert-butyl N-(but-3-en-1-yl)-N-methylcarbamateHCID 186245803-Bromo-5-(ethylthio)pyridine

Product 2

HCID 12717520(But-3-en-1-yl)(methyl)amineYield 97%HCID 18624577tert-butyl N-(but-3-en-1-yl)-N-methylcarbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

One representative compound, (E)-N-methyl-4-(3-[5-(ethylthio)pyridinyl])-3-buten-1-amine is prepared from N-methyl-N-(tert-butoxycarbonyl)-3-buten-1-amine and 3-bromo-5-(ethylthio)pyridine using the techniques set forth in W. C. Frank, et al., J. Org. Chem. 43(15):2947 (1978), and the tert-butoxy carbonyl protecting group is subsequently removed. Specifically, N-methyl-N-(tert-butoxycarbonyl)-3-buten-1-amine is prepared by (i) reacting 4-bromo-1-butene at 0.035 mole scale with a ten fold excess of condensed methylamine in N,N-dimethylformamide solvent in the presence of potassium carbonate to provide a 97% yield of N-mehtyl-3-buten-1-amine; (ii) the amine thus prepared is reacted at 0.030 mole scale with one equivalent of di-tert-butyldicarbonate in tetrahydrofuran to give N-methyl-N-(tert-butoxycarbonyl)-3-buten-1-amine in 68% yield. The 3-bromo-5-(ethylthio)pyridine is produced by the reaction of sodium ethanethiolate on 3,5-dibromopyridine in N,N-dimethylformamide in 86% yield. N-methyl-N-(tert-butoxycarbonyl)-3-buten-1-amine and 3-bromo-5-(ethylthio)pyridine are reacted using the Heck reaction on a 1.6 mmole scale in 2:1 acetonitrile:triethylamine using a catalyst consistingof one mole percent palladium acetate and four mole percent tri-o-tolylphosphine. N-methyl-N-(tert-butoxycarbonyl)-4-(3-[5-(ethylthio)pyridinyl])-3-buten-1-amine is obtained in 59% yield. Deprotection of the product may then be accomplished by 1:1 6N hydrochloric acid:tetrahdyrofuran.

Workup

  1. custom43(15):2947 (1978), and the tert-butoxy carbonyl protecting group is subsequently removed

Sources & evidence

ORD record
ord-d46b6a1c28c443b49a24a4b5c62f7a6f
Source dataset
uspto-grants-2001_08
Patent number
US06274606B1

Reaction notes

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